***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Sustained release or high levels of interleukin-1 ( IL-1 ) and /or tumor necrosis factor ( TNF ) , as observed after endotoxin challenge , can produce a variety of toxicities . Naturally occurring inhibitors to IL-1 and TNF , IL-1 receptor antagonist ( IL-1ra ) and soluble TNF receptor forms , have been detected . These proteins may function to buffer or limit the effects of these cytokines as part of a regulatory network . As part of a clinical trial of recombinant human interleukin-1 beta ( rhIL-1 beta ) , serial plasma sample s were obtained from 6 patients with metastatic melanoma treated with 30-min infusions of rhIL-1 beta for 5 consecutive days . The presence of circulating IL-1 receptor antagonist and soluble TNF binding proteins ( TNF-R55-BP and TNF-R75-BP ) were assessed . A maximum 86-fold increase for IL-1ra , a 7 - 8-fold increase for TNF-R55-BP , and a 2 - 3-fold increase for TNF-R75-BP were seen 2 - 4 h , 1 h , and 4 h , respectively , after rhIL-1 beta infusion . On each day of the treatment , the secretion of IL-1ra and release of TNF-R55-BP was observed , but there was no accumulation above baseline value for IL-1ra before each of the 5 daily infusions . Although there was a steady decrease of the 6-h postinfusion plasma levels for IL-1ra and TNF-R55-BP over the 5 treatment days , no increase of clinical side effects was noted . Two patients had measurable levels of TNF-alpha , but no correlation to TNF-binding proteins was observed . Our data show that early after rhIL-1 beta infusion the induction of IL-1ra secretion , as well as TNF-binding protein release , is observed Abstract Complex regional pain syndromes ( CRPS ) are characterized by persistent and severe pain after trauma or surgery . Neuro‐immune alterations are assumed to play a pathophysiological role . Here we set out to investigate whether patients with CRPS have altered systemic pro‐ and anti‐inflammatory cytokine profiles compared to controls on mRNA and protein level . We studied blood cytokine mRNA and protein levels of the pro‐inflammatory cytokines tumor necrosis factor‐α ( TNF ) , interleukin‐2 ( IL‐2 ) and IL‐8 and the anti‐inflammatory cytokines IL‐4 , IL‐10 , and transforming growth factor‐β1 ( TGFβ1 ) in 40 prospect ively recruited patients with CRPS I , two patients with CRPS II , and 34 controls .  Quantitative real‐time PCR and enzyme linked immunosorbent assay were used . Additionally , the patients underwent quantitative sensory testing and were assessed with the McGill pain question naire and the Hospital anxiety and depression scale  . Patients with CRPS had higher blood TNF and IL‐2 mRNA levels ( p = 0.005 ; p = 0.04 ) and lower IL‐8 mRNA levels ( p < 0.001 ) than controls . The mRNA for the anti‐inflammatory cytokines IL‐4 and IL‐10 was reduced in the patient group ( p = 0.004 ; p = 0.006 ) , whereas TGFβ1 mRNA levels did not differ between groups . These results were paralleled by serum protein levels , except for TGFβ1 , which was reduced in patients with CRPS , and for IL‐8 , which gave similar protein values in both groups . Sensory testing showed a predominant loss of small fiber‐related modalities in the patient group . The shift towards a pro‐inflammatory cytokine profile in patients with CRPS suggests a potential pathogenic role in the generation of pain Objectives Complex regional pain syndrome type 1 ( CRPS 1 ) is a disorder that can affect an extremity after minor trauma or surgery . The pathogenesis of this syndrome is unclear . It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response , but neurogenic dysregulation also may contribute to it . Methods For further insights into the pathogenesis of CRPS 1 , the authors investigated inflammatory and neurogenic mediators — C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) , soluble tumor necrosis factor receptor I/II ( sTNFR I/II ) ,  sE-selectin , sL-selectin , sP-selectin , substance P , neuropeptide Y , and calcitonin gene-related peptide — in  venous blood  from both the healthy arm and the arm with acute CRPS I from 25 patients and from 30 healthy volunteers . Results Levels of IL-8 and sTNFR I/II were significantly elevated in patients , whereas all soluble forms of selectins were significantly suppressed . There was no significant difference in white blood cell count ( WBC ) , CRP , and IL-6 . Substance P was significantly elevated in patients . The other two neuropeptides were unchanged . None of the parameters studied showed any differences between the CRPS I-affected arm and the normal arm . Conclusions Elevated IL-8 and sTNFR I/II levels indicate an association between CRPS I and an inflammatory process . Normal WBC , CRP , and IL-6 give evidence for localized inflammation . The hypothesis of neurogenic-induced inflammation mediated by neuropeptides is supported by elevated substance P levels We studied prospect ively the regional inflammatory response to a unilateral distal radial fracture in 114 patients at eight to nine weeks after injury and again at one year . Our aim was to identify patients at risk for a delayed recovery and particularly those likely to develop complex regional pain syndrome .  In order to quantify clinical ly the inflammatory response , a regional inflammatory score was developed . In addition , blood sample s were collected from the antecubital veins of both arms for comparative biochemical and blood-gas analysis . The severity of the inflammatory response was related to the type of treatment ( Kruskal-Wallis test , p = 0.002 ) . A highly significantly-positive correlation was found between the regional inflammatory score and the length of time to full recovery ( r(2 ) = 0.92 , p = 0.01 , linear regession ) . A regional inflammatory score of 5 points with a sensitivity of 100 % but a specificity of only 16 % also identified patients at risk of complex regional pain syndrome . None of the biochemical parameters studied correlated with regional inflammatory score or predicted the development of complex regional pain syndrome . Our study suggests that patients with a distal radial fracture and a regional inflammatory score of 5 points or more at eight to nine weeks after injury should be considered for specific anti-inflammatory treatment The aim of this study was to investigate whether interleukin (IL)-6 induces the production of IL-1 and tumor necrosis factor ( TNF ) antagonists . Serial plasma sample s were obtained from cancer patients participating in phase I and II trials of recombinant IL-6 administered as a 120-hour continuous intravenous ( IV ) infusion .  Plasma IL-1 receptor antagonist ( IL-1Ra ) and soluble TNF receptor p55 ( TNFsRp55 ) levels were measured by specific radioimmunoassays (  RIAs ) . IL-1Ra levels increased rapidly , reaching peak values ( 9.6 + /- 1.7 ng/mL ) within 2 to 4 hours of beginning treatment . Thereafter , levels promptly declined , reaching near baseline within 24 hours despite continuation of IL-6 . TNFsRp55 plasma levels increased within 4 to 8 hours after initiating treatment and increased progressively throughout the duration of therapy . IL-1 beta and TNF-alpha plasma levels were below the detection limit in all sample s tested . Peripheral blood mononuclear cells ( P BMC ) exposed to IL-6 produced only small amounts ( 1.56 + /- 0.3 ng/mL ) of IL-1Ra , even in the presence of exogenous soluble IL-6 receptor ( gp80 ) . TNFsRp55 levels measured in the supernatants of IL-6-stimulated P BMC were below the detection limit of the assay . Macrophages generated by culturing monocytes in granulocyte-macrophage colony-stimulating factor ( GM-CSF ) were much more responsive to IL-6 than freshly isolated unfractionated or adherent P BMC and synthesized almost as much IL-1Ra when stimulated with IL-6 as with endotoxin . These results suggest that the antinflammatory properties of IL-6 may be due ; in part , to the induction of IL-1Ra synthesis and the release of soluble TNF receptors . Our findings also suggest that tissue macrophages may be an important source of IL-6-induced IL-1Ra The clinical characteristics of complex regional pain syndrome (CRPS)--spontaneous and stimulus-evoked pain , autonomic abnormalities , motor dysfunction , and trophic changes in the affected limb -- are well known . However , its pathogenesis is unclear , and the diagnosis is often delayed , in part due to lack of objective laboratory tests . Endothelin-1 ( ET-1 ) is a potent vasoconstrictor that has recently been shown to produce pain , allodynia , edema , and muscle weakness , as well as to exert a direct excitatory effect on nociceptive afferents . Furthermore , new evidence indicates that ET-1 is involved in various cancer- and non-cancer-related painful conditions . The aim of the present explorative study was to determine the ET-1 plasma levels in patients with CRPS in an attempt to identify a ' laboratory marker ' for CRPS and to search for evidence suggesting that ET-1 may be involved in the pathogenesis of CRPS .  ET-1 plasma levels were determined in 20 severely affected CRPS patients , in eight patients with non-CRPS chronic painful conditions , and in 10 healthy volunteers . The results showed that there were no significant differences in ET-1 plasma levels between the three groups . We conclude that the plasma level of ET-1 can not be regarded as a ' marker ' for CRPS . Yet , the possibility that ET-1 is involved in the pathophysiology of CRPS has not been excluded and deserves further investigation 
    Output:
    
In acute CRPS , the concentrations of interleukin (IL)-8 and soluble tumor necrosis factor receptors I ( sTNF-RI ) and II ( sTNF-RII ) were significantly increased in blood .
Conclusion : CRPS is associated with the presence of a proinflammatory state in the blood , blister fluid , and CSF .
Different inflammatory profiles were found for acute and chronic cases