***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: Testosterone has immune-modulating properties , and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha , IL-1beta , and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10 . We report a r and omized , single-blind , placebo-controlled , crossover study of testosterone replacement ( Sustanon 100 ) vs. placebo in 27 men ( age , 62 + /- 9 yr ) with symptomatic and rogen deficiency ( total testosterone , 4.4 + /- 1.2 nmol/liter ; bioavailable testosterone , 2.4 + /- 1.1 nmol/liter ) . Compared with placebo , testosterone induced reductions in TNFalpha ( -3.1 + /- 8.3 vs. 1.3 + /- 5.2 pg/ml ; P = 0.01 ) and IL-1beta ( -0.14 + /- 0.32 vs. 0.18 + /- 0.55 pg/ml ; P = 0.08 ) and an increase in IL-10 ( 0.33 + /- 1.8 vs. -1.1 + /- 3.0 pg/ml ; P = 0.01 ) ; the reductions of TNFalpha and IL-1beta were positively correlated ( r(S ) = 0.588 ; P = 0.003 ) . In addition , a significant reduction in total cholesterol was recorded with testosterone therapy ( -0.25 + /- 0.4 vs. -0.004 + /- 0.4 mmol/liter ; P = 0.04 ) . In conclusion , testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol .  Twenty of these men had established coronary disease , and because total cholesterol is a cardiovascular risk factor , and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque , these properties may have particular relevance in men with overt vascular disease Post-chemotherapy treated cancer patients frequently report cognitive difficulties . The biology of this phenomenon is poorly understood , with uncertainty about possible direct toxic effects on the brain , secondary effects from systemic inflammation , host factors/genetic predisposition to cognitive complaints , or hormonal changes influencing cognitive function . To eluci date possible mechanisms associated with post-treatment cognitive dysfunction among breast cancer survivors , in 2007 we established a prospect i ve , longitudinal , observational cohort study of early stage breast cancer patients , recruited at the end of initial treatments ( primary treatment exposure included surgery , ± radiation , ± chemotherapy ) , and prior to the initiation of adjuvant endocrine therapy .  We assessed cognitive complaints , neuropsychological ( NP ) test performance , markers of inflammation , and brain imaging at baseline , 6 months and 12 months after enrollment . In this analysis of data from the first 93 patients enrolled in the cohort study , we focus on the relationship of circulating levels of proinflammatory cytokines to cerebral functioning and chemotherapy exposure . Among the proinflammatory cytokines tested ( IL-1 ra , sTNF-RII , CRP , and IL-6 ) at baseline , only sTNF-RII was increased among chemotherapy exposed patients , with a significant decline in the year after treatment ( p=0.003 ) . Higher baseline sTNF-RII in chemotherapy patients was significantly associated with increased memory complaints . In chemotherapy exposed patients , the longitudinal decline in sTNF-RII was significantly correlated with fewer memory complaints over 12 months ( r=-0.34 , p=0.04 ) . Higher baseline sTNF-RII was also associated with relatively diminished brain metabolism in the inferior frontal cortex ( r=-0.55 , p=0.02 ) , as well as relatively increased inferior frontal metabolism after 1 year , in chemotherapy-exposed subjects . These preliminary findings suggest that post-chemotherapy increases in TNF-α may be playing an important role in the manifestations of cognitive complaints in breast cancer survivors BACKGROUND Neuropsychological examinations have shown an elevated risk for cognitive impairment 2 years after therapy in breast cancer patients r and omized to receive adjuvant high-dose cyclophosphamide , thiotepa , carboplatin ( CTC ) chemotherapy  compared with a non-treated control group of stage I breast cancer patients . Patients r and omized to receive st and ard-dose fluorouracil , epirubicin , cyclophosphamide ( FEC ) chemotherapy showed no elevated risk compared with controls . However , breast cancer patients treated with conventional cyclophosphamide , methotrexate , 5-fluorouracil ( CMF ) chemotherapy showed a higher risk of cognitive impairment . The present study was design ed to obtain a greater insight into these long-term neuropsychological sequelae following chemotherapy and their course in time . PATIENTS AND METHODS At 4 years post-therapy , 22 of the original 34 CTC patients , 23 of 36  FEC patients , 31 of 39  CMF patients and 27 of 34  control patients were re-examined with neuropsychological tests . RESULTS Improvement in performance was observed in all chemotherapy groups , whereas in the control group there was a slight deterioration in test results . A differential attrition was observed among the groups , with a relatively high percentage of initially cognitively impaired patients from the CTC group dropping out due to factors related to disease progression . CONCLUSIONS The results suggest that cognitive dysfunction following adjuvant chemotherapy in breast cancer patients may be transient . Additional studies are needed to investigate the differential attrition of patients with cognitive impairment PURPOSE To examine the impact of age and cognitive reserve on cognitive functioning in patients with breast cancer who are receiving adjuvant treatments .  PATIENTS AND METHODS Patients with breast cancer exposed to chemotherapy ( n = 60 ; mean age , 51.7 years ) were evaluated with a battery of neuropsychological and psychological tests before treatment and at 1 , 6 , and 18 months after treatment . Patients not exposed to chemotherapy ( n = 72 ; mean age , 56.6 years ) and healthy controls ( n = 45 ; mean age , 52.9 years ) were assessed at matched intervals . RESULTS Mixed-effects modeling revealed significant effects for the Processing Speed and Verbal Ability domains . For Processing Speed , a three-way interaction among treatment group , age , and baseline cognitive reserve ( P < .001 ) revealed that older patients with lower baseline cognitive reserve who were exposed to chemotherapy had lower performance on Processing Speed compared with patients not exposed to chemotherapy ( P = .003 ) and controls ( P < .001 ) . A significant group by time interaction for Verbal Ability ( P = .01 ) suggested that the healthy controls and no chemotherapy groups improved over time . The chemotherapy group failed to improve at 1 month after treatment but improved during the last two follow-up assessment s. Exploratory analyses suggested a negative effect of tamoxifen on Processing Speed ( P = .036 ) and Verbal Memory ( P = .05 ) in the no-chemotherapy group . CONCLUSION These data demonstrated that age and pretreatment cognitive reserve were related to post-treatment decline in Processing Speed in women exposed to chemotherapy and that chemotherapy had a short-term impact on Verbal Ability . Exploratory analysis of the impact of tamoxifen suggests that this pattern of results may be due to a combination of chemotherapy and tamoxifen BACKGROUND Flu-like symptoms are common , early transient side effects of paclitaxel chemotherapy . We hypothesized that these symptoms may be due to release of inflammatory cytokines in response to treatment . The objective of this study was to assess changes in plasma levels of interleukin (IL)-1beta , IL-6 , IL-8 , IL-10 , IL-12 , and TNF-alpha during chemotherapy and to correlate these changes with musculoskeletal symptoms . METHODS Ninety patients with breast cancer were included ; 70 patients received single agent paclitaxel either weekly or every 3 weeks and 20 received FAC ( 5-FU , doxorubicin , cyclophosphamide ) chemotherapy . Fifteen healthy volunteers were included as controls .  Cytokines and symptoms were measured before starting therapy , on day 3 and on the last day of one treatment cycle . RESULTS At baseline , all subjects had measurable levels of IL-8 but only 49 % had IL-12 , 45 % had IL-10 , 32 % had IL-6 , and 21 % had IL-1beta or TNF-alpha in their plasma . There was no difference in baseline cytokine levels between cancer patients and the healthy volunteers . Schedule-dependent transient changes in the levels of 3 cytokines were observed in the paclitaxel treated patients . In the every 3-week paclitaxel group , IL-6 and IL-8 increased whereas in the weekly paclitaxel group IL-10 increased significantly compared to baseline . Fatigue and flu-like symptoms were also worse on day 3 . In the weekly paclitaxel group , increase in IL-10 level correlated positively with joint pain ( p=0.003 ) . In the every 3-week paclitaxel group , increase in IL-8 level correlated positively with flu-like symptom ( p=0.008 ) . In the FAC-treated group and among the healthy volunteers none of these cytokines increased significantly . CONCLUSIONS Weekly paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher dose treatments induce IL-8 and IL-6 in the plasma . These changes correlate with joint pain and flu-like symptoms Purpose : Clinical studies indicate that up to 70 % of patients with cancer who receive chemotherapy  experience cognitive impairment . The present study used a prospect i ve longitudinal design to assess short- and long-term effects of commonly used anticancer drugs on cognitive performance in a mouse model . Experimental Design : Normal mice received three weekly injections of a combination of methotrexate + 5-fluorouracil ( CHEMO group ) or an equal volume of saline ( SAL group ) . Cognitive tests , measuring different aspects of learning and memory , were administered before treatment , immediately after treatment , and three months later . Structural MRI scanning was conducted at each stage of cognitive testing . Results : The CHEMO group exhibited deficits on cognitive tasks acquired pretreatment [ spatial memory , nonmatching-to- sample ( NMTS ) learning , and delayed NMTS ] , as well as impaired new learning on two tasks ( conditional associative learning , discrimination learning ) introduced posttreatment . Consistent with clinical evidence , cognitive deficits were pronounced on tests that are sensitive to hippocampal and frontal lobe dysfunction , but the CHEMO group 's poor performance on the discrimination learning problem suggests that impairment is more widespread than previously thought . Cognitive deficits persisted for at least three months after treatment but some recovery was noted , particularly on tests thought to be under frontal lobe control . The MRI tests did not detect brain changes that could be attributed to treatment . Conclusions : Chemotherapeutic agents can have adverse effects on information acquired pretreatment as well as new learning and memory and , despite some recovery , impairment is long lasting . Clin Cancer Res ; 18(11 ) ; 3112–21 . © 2012 AACR 9008 Background : Cognitive complaints ( CC ) are common in BCS , and are associated with adjuvant chemotherapy ( CTx ) . The biology of these symptoms is poorly understood , enduring in 25 % of BCS . We tested the hypothesis that CTx-induced alterations in TNF inflammatory signaling might underlie observed cerebral dysfunction . METHODS We enrolled 93 BCS in a prospect i ve observational study within 1 month of completing primary treatment ( surgery , radiation , chemotherapy ) , prior to initiating endocrine therapy .  At entry , 6 and 12 months later , BCS completed self-report measures of CC and a 2 hr neuropsychological ( NP ) battery and had blood drawn for markers of proinflammatory cytokine activity : IL-6 , IL-1 receptor antagonist , soluble TNF receptor type 2 ( sTNFr2 ) , and C reactive protein . A subset of BCS ( n=14 ) had brain FDG-PET scans at entry and 12 mos . Multivariate models and ANOVA were used to examine relationships of cytokine activity with CC and CTx , controlling for covariates . RESULTS 53 % of BCS sample had received CTx . At entry , sTNFr2 was the only cytokine measure that was significantly elevated in CTx patients compared with non-CTx ( p=0.005 ) , and its level declined significantly by 12 months to a level similar to non CTx group ( p = 0.003 ) . CTx was also associated with increased CC at entry ( p=0.05 ) , controlling for time since CTx , age , IQ and BMI . CC were significantly associated with sTNFr2 ( p=0.05 ) at entry . Entry CC predicted subsequent NP test abnormalities at 6 months . PET scan sub study showed : among  CTx patients , higher levels of sTNFr2 correlated with lower levels of baseline metabolism in left inferior frontal gyrus , including Broca 's area ( p=0.002 ) . Entry sTNFr2 levels correlated with increases over 1 year in Broca 's area for the CTx group ( r=0.75 , p=0.02 ) , suggesting greater recovery of function in this area . CON 
    Output:
    
Weak to moderate correlations were observed between IL-1β , IL-6 , TNF-α levels , and different degrees of cognitive impairment .
Different types of chemotherapy treatments might lead to varying presentations and severities of cytokine-induced cognitive impairment .