<title>1. INTRODUCTION</title> <p>Acute pancreatitis is an important
and critical complication of endoscopic retrograde cholangiopancreatography
(ERCP) [##REF##1261883##1##]. The incidence of post-ERCP pancreatitis has been reported between 1% and 10% in various publications [##REF##12717271##2##]. ERCP is mostly performed on an
outpatient base. Therefore, early diagnosis of post-ERCP pancreatitis is
important for hospital admission and management. However, recognition of
post-ERCP pancreatitis based on clinical datas is not reliable [##REF##8759660##3##]. Several
biochemical and immunologic markers were determined as predictor of pancreatic
inflammation after ERCP [##REF##12432185##4##]. These markers are serum/urine amylase,
trypsinogen, trypsinogen activation peptide, C-reactive protein (CRP), and some
cytokines [##REF##12717271##2##, ##REF##12432185##4##].</p> <p>The studies show that the
serum levels of tumor necrosis factor <italic>α</italic> (TNF<italic>α</italic>), interleukin (IL)-1<italic>β</italic>, IL-6, and IL-8 are
significantly increased in acute pancreatitis [##REF##12717271##2##, ##REF##12432185##4##, ##REF##11435255##5##]. Pancreatic injury is mediated
by the release of these proinflammatory cytokines. After trypsinogen activation
into trypsin, a local inflammation is initiated which results in the local
production of inflammatory mediators [##REF##11435255##5##]. Interestingly, serum levels of
anti-inflammatory molecules such as IL-10, IL-1<italic>β</italic> receptor antagonist, and
soluble IL-2 receptor (sIL-2r) were also found significantly higher in patients
with acute pancreatitis [##REF##12432185##4##, ##REF##11435255##5##]. These findings support that these opposite
effective cytokines play roles together in the pathogenesis of acute
pancreatitis.</p> <p>A dynamic balance exists
between proinflammatory (pro-) and anti-inflammatory cytokines. The timing of
cytokine release, the local milieu, the presence of antagonistic or synergistic
factors, and the cytokine receptor density determines the net effect of
any cytokine [##REF##9646173##6##]. Polarization of T helper (Th) lymphocytes into functional Th1
and Th2 subsets is one of the main factors that determine the direction of the balance between
pro- and anti-inflammatory cytokines [##REF##2419430##7##, ##REF##7546192##8##]. While Th1 type cells produce high
levels of inflammatory cytokines including IL-2, TNF<italic>α</italic>, and interferon<italic>γ</italic> (IFN<italic>γ</italic>), Th2 type cells produce anti-inflammatory
cytokines including IL-4, IL-5, IL-6, IL-10, and IL-13 [##UREF##0##9##]. Both type cells
also produce lesser amounts of TNF<italic>α</italic>, granulocyte-macrophage colonystimulating
factor (GM-CSF), and IL-3 [##UREF##0##9##]. Th1-type cytokines are essential for the cell-mediated
immune responses against intracellular microorganisms [##UREF##1##10##]. However, Th2-type
cytokines participate in the development of humoral immunity against
extracellular microorganisms [##UREF##1##10##]. These 2-type cytokines have cross-regulatory
activity [##UREF##0##9##, ##UREF##1##10##]. IL-4 and IL-10 lead to the inhibition of
Th1-type immune responses by down-regulating the production of macrophage-derived
IL-12. Whereas, IFN<italic>γ</italic> alteres the balance of Th1-/Th2-type immune
responses in favour of Th1 by suppressing the Th2-type immune responses. It was
also known that the imbalance in the Th1/Th2 cytokine immune response is
related to the pathogenesis of some chronic inflammatory diseases such as
rheumatoid arthritis (RA), a Th1-type disease, and systemic lupus erythematosus
(SLE), a Th2-type disease [##REF##16704920##11##].</p> <p>The aim of this study was
to investigate the association between early changes (within 24 hours) in the
serum IL-2, IL-4, TNF<italic>α</italic>, and IL-6 concentrations and occurence of
subsequent pancreatitis complication after ERCP.</p>
<title>2. MATERIALS AND METHODS</title> <p>Forty five consecutive patients (20 men and 25 women; mean age: 54.8 years; SD:15.9) who underwent therapeutic ERCP
were enrolled to the study. Exclusion and inclusion criteria of this study are detailed
in ##TAB##0##Table 1##. Control group consisted of 10 patients with acute pancreatitis
without ERCP (7 men and 3 women; mean age: 48.7 years; SD:17.3). Etiological
factors in the control group were gallstones in 4, drug useage in 3, and
alcohol in 2 patients. A certain etiological factor could not be determined in
1 patient.</p> <p>All the patients who
underwent ERCP had normal serum levels of CRP and amylase, before ERCP
procedure. Serum concentrations of IL-2, IL-4, TNF<italic>α</italic>, and IL-6 were determined immediately before
12 hours and 24 hours after ERCP. ERCP was performed by the same operator after
premedication. Olympus JF-240 electronic duodenoscope (Olympus Optical Co.,
Ltd, Tokyo, Japan) was used for ERCP.
Radiologic images were taken by using C-arm x-ray device (Philips, BV 300, Philips Medical Systems, Best, The Netherlands). Antibiotic prophylaxis with Cephazolin Sodium was started for all patients undergoing ERCP. After an overnight
fast, all patients were sedated with 10 mg i.v. dormicum. For cytokine
measurements, serum samples from each patient were stored at −70°C until run. However
serum amylase and CRP levels were determined on the day of sampling. Serum amylase
levels were determined by enzymatic color test and upper limit of normal range was accepted as 90 L/U according
to our laboratory standarts. Serum CRP levels were measured using a
nephelometer (Behring BN II Analyzer, Dade Behring, Marburg, Germany) and the high-sensitivity
reagent kit. A level &lt;6 mg/L for CRP was accepted as normal. Serum levels of
IL-2, IL-4, TNF<italic>α</italic>, and IL-6 were determined using ELISA kits (Bender
MedSystems GmbH, Vienna, Austria). Interassay and
intra-assay coefficients of variation for each assay were, respectively, as
follows: 8 and 5.2% for IL-2; 5.6 and 4.8% for IL-4; 7.4 and 6.9% for TNF<italic>α</italic>; and 5.2 and 3.4% for IL-6.</p> <p>The diagnostic criteria
for post-ERCP pancreatitis were epigastric pain during 24 hours after ERCP, at
least three-fold increase in upper limit of normal level of serum amylase and/or
acute pancreatitis seen in the abdominal ultrasonography and computed
tomography [##REF##12432186##12##]. All patients were informed about the aim and procedures of the
study and gave their consent. The study was approved by the Ethical Committee
of Gulhane Military School of Medicine.</p> <p>All statistical analyses
were performed using SPSS (SPSS 11.5, SPSS Inc., Chicago, IL, USA) statistical package. For the tests
of normality, we used Kolmogorov-Smirnov test. Results are expressed as median
(range). The Friedman test was used for multiple statistical comparisons. The
Wilcoxon test was used as a post hoc test if the Friedman test is statistically
significant. Mann-Whitney U test was used to compare the mean or median values
of cytokines, CRP, and amylase in blood in the various study groups. To
investigate the relations among the variables, we used Pearson or Spearman's
rank correlation test, which was appropriate. A <italic>P</italic> value &lt; .05 was considered
to be statistically significant.</p>
<title>3. RESULTS</title> <p>Seven of the 45 patients (15.5%)
developed post-ERCP pancreatitis. Two of them had severe pancreatitis and 5
patients had mild disease according to Atlanta
criteria [##REF##8489394##13##]. First symptoms were occured a mean of 5.2 hours after ERCP in
these 7 patients.</p> <p>Serum amylase levels at
12 and 24 hours after ERCP were significantly higher in the patients with
post-ERCP pancreatitis than in those without pancreatitis (##TAB##1##Table 2##). The levels
of amylase were also significantly higher in the control group with acute
pancreatitis than in those of the levels before and after ERCP in the patients
without post-ERCP pancreatitis. While serum amylase levels before and 24 hours
after ERCP were significantly lower in the patients with post-ERCP pancreatitis
than those of the control group with acute pancreatitis, the amylase levels at
12 hours after ERCP in the patients with post-ERCP pancreatitis were not
different from those of the control group with acute pancreatitis. CRP levels
before and within 24 hours after ERCP in the patients who underwent ERCP and those
of the control group with acute pancreatitis were not different from one other.
In serial measurements of complicated and uncomplicated patients, serum amylase
levels at 12 and 24 hours after ERCP were higher than those of the basal levels
(<italic>P</italic> = .018 and <italic>P</italic> &lt; .001, resp.), and the levels of amylase at 24 hours
after ERCP were also higher than those of the levels at 12 hours after ERCP
(<italic>P</italic> = .018 and <italic>P</italic> &lt; .001, resp.). There was no significant difference among
the CRP levels in the serial measurements of complicated and uncomplicated
patients.</p> <p>Significant differences
in IL-4, IL-6 and TNF<italic>α</italic> levels at 12 and 24 hours after ERCP were
found among the patients who underwent ERCP and the control group patients. The
levels of IL-4 at 24 hours after ERCP in the patients with post-ERCP
pancreatitis and the control group patients were significantly lower than in
those without ERCP-induced pancreatitis (##TAB##1##Table 2##, 
##FIG##0##Figure 1(a)##). While TNF<italic>α</italic> levels in the control group patients were
higher than those of the levels before ERCP in the patients with and without
post-ERCP pancreatitis (##TAB##1##Table 2##, ##FIG##0##Figure 1(b)##), the levels of TNF<italic>α</italic> at 12 hours after ERCP in the patients with
and without post-ERCP pancreatitis were not different from the control patients
(##TAB##1##Table 2##, ##FIG##0##Figure 1(c)##).
However those TNF<italic>α</italic> levels in the complicated group were higher
than those of the levels at 12 hours after ERCP in the uncompicated group
(##TAB##1##Table 2##, ##FIG##0##Figure 1(c)##).
There was no other significant difference among complicated and uncomplicated
patients before and within 24 hours after ERCP and control group patients with
respect to serum IL-4 and TNF<italic>α</italic> concentrations. Addionally, IL-2 levels before
and within 24 hours after ERCP in the complicated and uncomplicated patients
and the control patients were not different from one another. While the levels
of IL-6 were higher in the control group patients than those of the levels
before and 12 hours after ERCP in both patients group who underwet ERCP (##TAB##1##Table 2##, Figures ##FIG##0##1(d)##, ##FIG##0##1(e)##), IL-6 levels at 24 hours after ERCP in the patients with
post-ERCP pancreatitis were not different from the control patients but higher
than those of the patients without post-ERCP pancreatits (##TAB##1##Table 2##, ##FIG##0##Figure 1(f)##). On the other hand, the
ratios of TNF<italic>α</italic>/IL-4 at 12 and 24 hours after ERCP were found
significantly higher in the complicated patients than those of the
uncomplicated patients but not diffrent from the control patients (##TAB##1##Table 2##,
Figures ##FIG##0##1(g)##, ##FIG##0##1(h)##). There was not any difference with respect to IL-2/IL-4 ratio
among all patient groups.</p> <p>Statistical significant differences
were observed among the levels of IL-4, TNF<italic>α</italic>, and IL-6 in serial measurements before and within 24
hours after ERCP in the patients who underwent ERCP (##TAB##1##Table 2##, ##FIG##1##Figure 2##). In the
patients with post-ERCP pancreatitis and without pancreatitis, significantly
higher levels of TNF<italic>α</italic> and IL-6 were found at 12 hours after ERCP compared
to the levels before ERCP. In the patients without post-ERCP pancreatitis, the
levels of IL-4, TNF<italic>α</italic>, and IL-6 at 24 hours after ERCP were also higher
than those of the basal levels. However, in the complicated group, only IL-6
levels at 24 hours after ERCP were higher than the basal levels.</p> <p>In the complicated
patients, basal IL-6 levels positively correlated with basal CRP levels, but
negatively correlated with basal IL-4 levels (<italic>r</italic> = 0.812; <italic>P</italic> = .048, <italic>r</italic> = 0.847;
<italic>P</italic> = .016, resp.). In the complicated patients, IL-4 and CRP levels at 24
hours after ERCP were also negatively correlated with each other (<italic>r</italic> = 0.900;
<italic>P</italic> = .037). In the patients without post-ERCP pancreatitis, a positive correlation
was found between IL-4 and TNF<italic>α</italic> levels at 24 hours after ERCP (<italic>r</italic> = 0.397; <italic>P</italic> = .018),
but there was a negative correlation between IL-4 and IL-6 levels at 12 hours
after ERCP (<italic>r</italic> = 0.392; <italic>P</italic> = .018).</p>
<title>4. DISCUSSION</title> <p>Acute pancreatitis is the most
common serious complication of ERCP [##REF##1261883##1##]. The incidence of post-ERCP
pancreatitis was found 15.5% in our study. This incidence is comparable to that
(2 to 15%) of other reports [##REF##11232684##14##, ##REF##16405547##15##].</p> <p>In our study, serum 
amylase levels at 12 and 24 hours after ERCP were significantly higher in the
patients with post-ERCP pancreatitis than in those without pancreatitis. Additionally,
the levels of amylase were also significantly higher in the control group with
acute pancreatitis than in those of the levels before and 24 hours after ERCP and
those of the levels before and within 24 hours after ERCP in the patients with
post-ERCP pancreatitis and without pancreatitis, respectively, but not
different from those of the levels 12 hours after ERCP in the complicated group.
Hyperamylasemia associated with abdominal pain has been evaluated as a reliable
indicator of post-ERCP pancreatitis [##REF##17569133##16##, ##REF##11154486##17##]. However, serum amylase levels are
commonly elevated in uncomplicated ERCPs. Therefore, it seems that serum
amylase measurement alone is not a well indicator in predicting the development
of pancreatitis after ERCP. In our study, increased amylase levels at 12 and 24
hours after ERCP were found in serial measurements of patients with post-ERCP
pancreatitis and without pancreatitis compared to the basal levels. The levels
of amylase at 24 hours after ERCP in both patient groups were also higher than
those of the levels at 12 hours after ERCP. The serial changes of amylase
levels in patients without pancreatitis suggest the existance of subclinical
pancreatic damage. It is well known that serum amylase levels rise in reaction
to manipulations during ERCP in the majority of patients [##REF##12432185##4##].</p> <p>C-reactive protein (CRP)
is one of the acute-phase reactant that increases during systemic 
inflammation. We did not find any significant difference in the levels of CRP before and
after ERCP in comparison between patients with post-ERCP pancreatitis and
without pancreatitis or among serial measurements of complicated and
uncomplicated patients. CRP levels in both ERCP groups were also not different
from the control group patients. Our findings may be explained by CRP being a late marker
in the laboratory monitoring of post-ERCP pancreatitis [##REF##11577303##18##]. Its changes are
commonly initiated at least 24 hours after ERCP [##REF##12432185##4##]. However, we did not
investigate the changes of CRP levels in the late phase after ERCP. Therefore,
our results showed that CRP does not increase in the early phase after ERCP.</p> <p>There are several
speculative conclusions related to cytokine investigations in ERCP in the
literature. Our study provides a new insight in ERCP-induced pancreatitis with
regard to results. We found that the levels of TNF<italic>α</italic> were increased at 12 hours after ERCP in the
patients with post-ERCP pancreatitis compared with those of the patients
without pancreatitis. There was no significant difference in TNF<italic>α</italic> concentrations before and 24 hours after ERCP between
complicated and uncomplicated patients. In Chen et al.'s study, TNF<italic>α</italic> was found significantly increased at 8 and 24
hours after ERCP in the patients with post-ERCP pancreatitis [##REF##12717271##2##]. However,
Messmann et al. did not find
significant difference in the TNF<italic>α</italic> measurements of patients with post-ERCP
pancreatitis [##REF##9155580##19##].</p> <p>We found that the serum
levels of IL-4 at 24 hours after ERCP were lower in the patients with post-ERCP
pancreatitis and control group patients than in those of the patients without
post-ERCP pancreatitis. It is well known that IL-4 plays a crucial role in Th2-cell
development [##UREF##0##9##, ##UREF##1##10##]. Additionally, IL-4 has potent anti-inflammatory properties
and inhibits secretion of IL-1<italic>β</italic> and TNF<italic>α</italic> by monocytes. It may be said that low level of
IL-4 in the patients with post-ERCP panceratitis and control patients causes the
relative or absolute dominance of inflammatory state. We investigated the serum
levels of inflammatory cytokines including IL-2, TNF<italic>α</italic>, IL-6 and IL-2/IL-4, and TNF<italic>α</italic>/IL-4 ratios before and after ERCP in order to identify
the dominance of inflammatory or anti-inflammatory state at different time points
of ERCP. According to our results, neither IL-2 levels nor IL-2/IL-4 ratios
were different from one another among the patients who underwent ERCP and the
control patients. Although there is not any report on IL-2 levels in before and
after ERCP, increased sIL-2r levels was observed in a study in the patients
with acute panceratitis [##REF##10986216##20##]. We did not also find any report investigating the
relation between IL-4 and ERCP in the literature. However, in Chen et al.'s
study, the other anti-inflammatory cytokine IL-10 was reported as a marker with
respect to reflect the severity of acute pancreatitis [##REF##10562589##21##]. This study seems contrary
to our study with regard to indicating the dominance of an anti-inflammatory state
after ERCP.</p> <p>In our study, the
evidences suggested TNF<italic>α</italic> dominance in the patients with post-ERCP pancreatitis
were high levels of TNF<italic>α</italic> at 12 hours after ERCP and high ratio of TNF<italic>α</italic>/IL-4 at 12 and 24 hours after ERCP. The levels
of TNF<italic>α</italic> at 12 hours after ERCP in the complicated
patients were not different from the control patients. These findings are compatible with the studies
reported by Chen et al. [##REF##12717271##2##] and Devière et al. [##REF##11159890##22##] but contrary to
Oezcueruemez-Porsch et al.'s study [##REF##9724166##23##]. In the first study, the levels of TNF<italic>α</italic> were
reported to be significantly increased at 8 and 24 hours after ERCP in the
patients with post-ERCP pancreatitis [##REF##12717271##2##]. The increased TNF<italic>α</italic> levels in patients with post-ERCP pancreatitis
were also observed in Devière et. al.'s study. However, TNF<italic>α</italic> levels at any time of ERCP were not detectable
in the patients with evidence of ERCP-induced pancreas damage. Although some
controversial results in the literature, our findings together with Chen et.
al.'s study suggest that there was a bias towards increase of TNF<italic>α</italic> within 24 hours after ERCP.</p> <p>In our study, IL-6
levels at 24 hours after ERCP in the patients with post-ERCP pancreatitis were
not different from the control group patients but higher than those of the patients
without post-ERCP pancreatits. However IL-6 levels before and 12 hours after
ERCP in both patients with ERCP-induced pancreatitis and without pancreatitis
were not observed differently from each other. As compatible with our results,
in many studies, IL-6 has been reported as a good predictor for the development
of pancreatitis after ERCP [##REF##12717271##2##, ##REF##12432185##4##, ##REF##9724166##23##, ##REF##10508122##24##].</p> <p>We observed that the
serial changes occur in IL-4, TNF<italic>α</italic>, and IL-6 after ERCP. According to our
findings, TNF<italic>α</italic> and IL-6 levels in the complicated patients were
found to be incerased at 12 hours after ERCP compared to those of the basal
levels. In the complicated patients, IL-6 levels at 24 hours after ERCP were
also higher than those of the basal levels. Besides the increased levels of TNF<italic>α</italic> and IL-6 at 12 and 24 hours after ERCP were
found in our uncomplicated patients compared to those of the basal levels, the
levels of IL-4 were also found increased at 24 hours after ERCP than those of
the basal levels. Our results related to the serial measurements of the cytokines
support the
existance of inflammatory activity and subclinical pancreatic damage in
patients without ERCP-induced pancreatitis. Our findings with respect to serial
IL-6 changes are compatible with the studies reported by Chen et al. [##REF##12717271##2##] and Messmann et al. [##REF##9155580##19##]. In their studies, maximal concentration of IL-6 in the ERCP procedure was
found 24 hours after ERCP.</p> <p>We observed reasonable
correlations among the measured parameters in the patients with or without ERCP-induced
pancreatitis. CRP was negatively correlated with IL-4 levels at 24 hours after
ERCP in the patients with post-ERCP pancreatitis that supports the dominance of
inflammatory activity at this time after ERCP. Surprisingly, basal IL-6 levels in
the patients with post-ERCP pancreatitis positively correlated with basal CRP
levels, but negatively correlated with basal IL-4 levels. On the other hand, IL-4
positively correlated with TNF<italic>α</italic> at 24 hours after ERCP in the uncomplicated
patients, but negatively correlated with IL-6 at 12 hours after ERCP. These
findings indirectly support the existance of systemic immune activation in the
patients without ERCP-induced pancreatitis. Diffrerent results related to the
correlations among the cytokines, pancreatic enzymes, and CRP levels in the ERCP
procedure were reported in the literature. In the Chen et al.'s study, serum
IL-6 was found significantly correlated with serum amylase at 8 and 24 hours
after ERCP [##REF##12717271##2##]. In another study, serum matrix metalloproteinase 9 (MMP9) level
in severe acute pancreatitis was positively correlated with TNF<italic>α</italic> and CRP levels [##REF##16498235##25##].</p>
<title>5. CONCLUSIONS</title> <p>In conclusion, the enhancement of
serum TNF<italic>α</italic> and IL-6 levels in the patients with ERCP-induced
pancreatitis reflects the inflammatory activity. Additionally, IL-4, IL-6, and
TNF<italic>α</italic> can be used in clinical laboratory monitoring
of ERCP. However, it should be considered that the Th1 or Th2 cytokine
dominance before and after ERCP is one of the main factors determining the
balance between pro- and anti-inflammatory statuses of organism. Some
conflicting cytokine results about ERCP-induced pancreatitis in the literature
may depend on the direction of Th polarization at the sampling time for serum
cytokine levels. Therefore, the other Th cytokines (IFN<italic>γ</italic>, IL-12, IL-18, IL-5, IL-13) may influence the inflammatory
activity after ERCP, and can be a topic of the future study. In addition, it
seems that the presenting the cytokine profile is important to effective
usage of anti-inflammatory cytokines and cytokine inhibitors in ERCP-induced
pancreatitis. On the other hand, monitoring interval in the post-ERCP period
should be longer than 24 hours.</p>
<p>Recommended by Shyam Mohapatra</p> <p>
<italic>Background</italic>. Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits. <italic>Goals</italic>. To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)<italic>α</italic>, and IL-6 levels and the development of post-ERCP pancreatitis. <italic>Study</italic>. Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNF<italic>α</italic>, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP. <italic>Results</italic>. Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNF<italic>α</italic> levels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNF<italic>α</italic>/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP. <italic>Conclusions</italic>. The enhancement of serum TNF<italic>α</italic> and IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP.</p>
<fig id="fig1" position="float"><label>Figure 1</label><caption><p>The levels of IL-4 (a) and TNF (b), (c), IL-6 (d), (e), (f) and the ratios of TNF/IL-4 (g), (h) in the patients with ERCP-induced pancreatitis (EIP+), patients without ERCP induced pancreatitis (EIP−), and the control group (CG) with acute pancreatitis without ERCP. Boxes show the ranges of 1st and 3rd quartiles and extreme values. Horizontal bars represent median values. The differences between two groups were evaluated by Mann-Whitney U test. <italic>P</italic> values were indicated above the boxes when a level of significance less than or equal to .05 was reached in comparisons of study groups.</p></caption></fig> <fig id="fig2" position="float"><label>Figure 2</label><caption><p>Serial concentrations of IL-2, IL-4, TNF and IL-6 before and within 24 hours after ERCP
in the patients (a) with
post-ERCP pancreatits and (b) without pancreatitis. Bars represent mean ± 95% CI. The differences between two groups were
evaluated by Mann-Whitney U test. <italic>P</italic> values were
indicated above the boxes when a level of significance less than or equal
to .05 was reached in comparisons of study groups.
</p></caption></fig>
<table-wrap id="tab1" position="float"><label>Table 1</label><caption><p>Exclusion and inclusion criteria of the patients.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"> Exclusion criteria </th><th align="left" rowspan="1" colspan="1"> Inclusion criteria </th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Emergency ERCP</td><td align="left" rowspan="1" colspan="1">Choledocholithiasis</td></tr><tr><td align="left" rowspan="1" colspan="1">Previous therapeutic ERCP</td><td align="left" rowspan="1" colspan="1">Pancreato-biliary malignancy</td></tr><tr><td align="left" rowspan="1" colspan="1">Previous surgery of the upper GI
tract</td><td align="left" rowspan="1" colspan="1">Cholestasis of unknown origin</td></tr><tr><td align="left" rowspan="1" colspan="1">Acute pancreatitis at time of
study</td><td align="left" rowspan="1" colspan="1">Cholangitis</td></tr><tr><td align="left" rowspan="1" colspan="1">Known history of chronic
pancreatitis</td><td align="left" rowspan="1" colspan="1">Tumor of papilla</td></tr><tr><td align="left" rowspan="1" colspan="1">Less than 18 years of age</td><td align="left" rowspan="1" colspan="1">Others</td></tr><tr><td align="left" rowspan="1" colspan="1">Known history of mental disease</td><td align="left" rowspan="1" colspan="1"/></tr><tr><td align="left" rowspan="1" colspan="1">Unable to give informed consent</td><td align="left" rowspan="1" colspan="1"/></tr><tr><td align="left" rowspan="1" colspan="1">Female who is pregnant</td><td align="left" rowspan="1" colspan="1"/></tr><tr><td align="left" rowspan="1" colspan="1">Underlying chronic liver disease</td><td align="left" rowspan="1" colspan="1"/></tr><tr><td align="left" rowspan="1" colspan="1">Abnormal coagulation tests
(PTT &lt; 75% or INR &gt; 1.5 or APTT &gt; 35)</td><td align="left" rowspan="1" colspan="1"/></tr><tr><td align="left" rowspan="1" colspan="1">Immunocompromized patients</td><td align="left" rowspan="1" colspan="1"/></tr></tbody></table></table-wrap> <table-wrap id="tab2" position="float"><label>Table 2</label><caption><p>Comparisons of IL-2, IL-4, TNF<italic>α</italic>, IL-6, CRP and amylase levels and IL-2/IL-4
and TNF<italic>α</italic>/IL-4 ratios in the patients who underwent ERCP
and control group with acute pancreatitis without ERCP.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"/><th align="center" colspan="3" rowspan="1">Patients with post-ERCP pancreatitis (<italic>n</italic> = 7) <bold>(1)</bold>
</th><th align="center" colspan="3" rowspan="1">Patients without pancreatitis (<italic>n</italic> = 38) <bold>(0)</bold>
</th><th align="left" rowspan="1" colspan="1">Patients with acute pancreatitis without ERCP (<italic>n</italic> = 10) <bold>(2)</bold>
</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Time (hour)</td><td align="left" rowspan="1" colspan="1">
<bold>0.</bold>
</td><td align="left" rowspan="1" colspan="1">
<bold>12.</bold>
</td><td align="left" rowspan="1" colspan="1">
<bold>24.</bold>
</td><td align="left" rowspan="1" colspan="1">
<bold>0.</bold>
</td><td align="left" rowspan="1" colspan="1">
<bold>12.</bold>
</td><td align="left" rowspan="1" colspan="1">
<bold>24.</bold>
</td><td align="left" rowspan="1" colspan="1"/></tr><tr><td align="left" rowspan="1" colspan="1">IL-2 (pg/mL)</td><td align="left" rowspan="1" colspan="1">15.6 (19.9)</td><td align="left" rowspan="1" colspan="1">14.3 (14.1)</td><td align="left" rowspan="1" colspan="1">12.7 (15.5)</td><td align="left" rowspan="1" colspan="1">15.1 (43.9)</td><td align="left" rowspan="1" colspan="1">12.7 (76.0)</td><td align="left" rowspan="1" colspan="1">15.1 (46.0)</td><td align="left" rowspan="1" colspan="1">11.4 (13.0)</td></tr><tr><td align="left" rowspan="1" colspan="1">IL-4 (pg/mL)</td><td align="left" rowspan="1" colspan="1">29.0 (69.1)</td><td align="left" rowspan="1" colspan="1">63.6 (67.5)</td><td align="left" rowspan="1" colspan="1">
<bold>37.7 (56.4)</bold>
<sup>(a)</sup>
</td><td align="left" rowspan="1" colspan="1">37.7 (146.8)</td><td align="left" rowspan="1" colspan="1">55.9 (83.8)</td><td align="left" rowspan="1" colspan="1">
<bold>63.6 (98.0)</bold>
<sup>(b)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>37.9 (58.4)</bold>
<sup>(c)</sup>
</td></tr><tr><td align="left" rowspan="1" colspan="1">TNF<italic>α</italic> (pg/mL)</td><td align="left" rowspan="1" colspan="1">20.2 (67.8)</td><td align="left" rowspan="1" colspan="1">
<bold>82.9 (81.9)</bold>
<sup>(f)</sup>
</td><td align="left" rowspan="1" colspan="1">44.9 (77.5)</td><td align="left" rowspan="1" colspan="1">
<bold>18.6 (66.9)</bold>
<sup>(d)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>43.6 (90.5)</bold>
<sup>(g)</sup>
</td><td align="left" rowspan="1" colspan="1">51.8 (72.1)</td><td align="left" rowspan="1" colspan="1">
<bold>50.3 (77.5)</bold>
<sup>(e)</sup>
</td></tr><tr><td align="left" rowspan="1" colspan="1">IL-6 (pg/mL)</td><td align="left" rowspan="1" colspan="1">
<bold>1.2 (1.4)</bold>
<sup>(h)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>2.4 (1.9)</bold>
<sup>(k)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>3.4 (6.4)</bold>
<sup>(m)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>1.6 (5.8)</bold>
<sup>(j)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>2.4 (10.5)</bold>
<sup>(l)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>1.9 (7.3)</bold>
<sup>(n)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>5.2 (9.8)</bold>
<sup>(i)</sup>
</td></tr><tr><td align="left" rowspan="1" colspan="1">IL-2/IL-4</td><td align="left" rowspan="1" colspan="1">0.62 (2.03)</td><td align="left" rowspan="1" colspan="1">0.33 (2.30)</td><td align="left" rowspan="1" colspan="1">0.40 (0.90)</td><td align="left" rowspan="1" colspan="1">0.44 (26.81)</td><td align="left" rowspan="1" colspan="1">0.24 (2.61)</td><td align="left" rowspan="1" colspan="1">0.23 (0.71)</td><td align="left" rowspan="1" colspan="1">0.3 (0.61)</td></tr><tr><td align="left" rowspan="1" colspan="1">TNF<italic>α</italic>/IL-4</td><td align="left" rowspan="1" colspan="1">0.56 (10.0)</td><td align="left" rowspan="1" colspan="1">
<bold>1.31 (5.77)</bold>
<sup>(o)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>1.18 (2.80)</bold>
<sup>(r)</sup>
</td><td align="left" rowspan="1" colspan="1">0.67 (91.83)</td><td align="left" rowspan="1" colspan="1">
<bold>0.82 (3.38)</bold>
<sup>(p)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>0.81 (1.35)</bold>
<sup>(s)</sup>
</td><td align="left" rowspan="1" colspan="1">1.0 (1.53)</td></tr><tr><td align="left" rowspan="1" colspan="1">CRP (mg/dL)</td><td align="left" rowspan="1" colspan="1">10.2 (49)</td><td align="left" rowspan="1" colspan="1">17.0 (33)</td><td align="left" rowspan="1" colspan="1">10 (47)</td><td align="left" rowspan="1" colspan="1">3.9 (212)</td><td align="left" rowspan="1" colspan="1">8.0 (395)</td><td align="left" rowspan="1" colspan="1">6.7 (342)</td><td align="left" rowspan="1" colspan="1">12.0 (42)</td></tr><tr><td align="left" rowspan="1" colspan="1">Amylase (U/mL)</td><td align="left" rowspan="1" colspan="1">
<bold>50 (74)</bold>
<sup>(t)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>1114 (1806)</bold>
<sup>(x)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>460 (552)</bold>
<sup>(z)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>47 (179)</bold>
<sup>(v)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>131 (673)</bold>
<sup>(y)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>79 (290)</bold>
<sup>(zz)</sup>
</td><td align="left" rowspan="1" colspan="1">
<bold>1357 (2558)</bold>
<sup>(u)</sup>
</td></tr></tbody></table></table-wrap>
<table-wrap-foot><fn><p>
<italic>P</italic> values: .010 for (a) versus (b); .025 for (b)
versus (c); .002 for (d) versus (e); .011 for (f) versus (g); .001 for
(h) versus (i); &lt;.001 for (j) versus (i); .014 for (k) versus (i); 
.012 for (l) versus (i); .034 for (m) versus (n); .001 for (n) versus
(i); .028 for (o) versus (p); .041 for (r) versus (s); .001 for (t)
versus (u); &lt;.001 for (v) versus (u); &lt;.001 for (x) versus
(y); &lt;.001 for (y) versus (u); &lt;.001 for (z) versus (zz); 
&lt;.001 for (zz) versus (u); .001 for (z) versus (u).</p></fn></table-wrap-foot>
<graphic xlink:href="CDI2008-481560.001"/> <graphic xlink:href="CDI2008-481560.002"/>
[{"label": ["9"], "surname": ["Abbas", "Lichtman", "Abbas", "Lichtman"], "given-names": ["AK", "AH", "AK", "AH"], "article-title": ["Cytokines"], "italic": ["Cellular and Molecular Immunology"], "year": ["2003"], "edition": ["5th edition"], "publisher-loc": ["Philadelphia, Pa, USA"], "publisher-name": ["Saunders"], "fpage": ["243"], "lpage": ["274"], "comment": ["chapter 11."]}, {"label": ["10"], "surname": ["Abbas", "Lichtman", "Abbas", "Lichtman"], "given-names": ["AK", "AH", "AK", "AH"], "article-title": ["Immunity to microbes"], "italic": ["Cellular and Molecular Immunology"], "year": ["2003"], "edition": ["5th edition"], "publisher-loc": ["Philadelphia, Pa, USA"], "publisher-name": ["Saunders"], "fpage": ["345"], "lpage": ["366"], "comment": ["chapter 15."]}]
Clin Dev Immunol. 2008 Jul 21; 2008:481560