Chronic Social Restriction Stress Impacts On Human Serum Cytokines

Objectives: According to a longitudinal study of social restriction stress, we studied the impactof chronic stress on various human serum cytokines and search for the potential biomarker forchronic stress.Methods: We recruited10social participants to receive the chronic social restriction stressresearch of6phases in a room with50m2, in the end of each phase, the subjects could go out ofthe room without restriction with3days and then enter the next phase. All the experiments lasted150days and subjects were provied adequate nutrition, facilities for creation and exercise.150days after the experiment,7subjects were followed up. In each phase of the study, hostility scoreand anxiety score were measured and blood was sampled at7to8am at1day before theexperiment,21days,90days and150days after the experiment and follow up. ELISA kit wereused to quantitative measure the concentration of serum cortisol. Ultra-sensitive ELISA kit wereused to quantitative measure the concentration of serum IL-6. Luminex Microsphereassays usedto quantitative measure the concentration of serum various cytokines. The impact of chronicstress on subject serum cortisol and cytokines were analyzed and ROC curve analys is were usedto evaluate the diagnostic value of the cytokines for chronic stress.Results:1. The impact of chronic stress on subjects’hostility and anxiety: The hostility score and anxietyscore elevated during chronic stress, even no significant difference were found(p>0.05).2. The impact of chronic stress on subjects’serum cortisol: Serum cortisol level of subjects waselevated significantly at day90(p<0.05) and then recovered to baseline level(p>0.05).3. The impact of chronic stress on subjects’serum interleukin: Serum IL-6and IL-7level wassignificantly decreased respectively at day90(p<0.05) and day150(p<0.01); No significantchange was observed with IL-12and IL-17.4. The impact of chronic stress on subjects’serum growth factor: EGF, VEGF and FGF-2 significantly elevated at day90(p<0.01, p<0.05and p<0.05, respectively), while the EGF levelwas already increased at day21(p<0.05); Serum TGF-α level decreased under stress and lowestat day150(p<0.01).5. The impact of chronic stress on subjects’serum chemokines: IL-8, GRO and MIP-1αsignificantly decreased all the time during stress(IL-8: p<0.01, p<0.01, p<0.01; GRO: p<0.05,p<0.05, p<0.01; MIP-1α: p<0.001, p<0.01, p<0.001, respectively); IP-10level increasedsignificantly at day21and90(p<0.05); MIP-1β and MDC level decreased significantly at day150(p<0.01and p<0.001respectively); No significant change was observed withFractalkine(p>0.05).6. Follow up recovery: All the cytokines recovered to baseline level except IL-7and MDC atfollow up(p<0.01, p<0.05respectively).7. Potential biomarkers for chronic stress: MIP-1α, IL-8, MDC, GRO, IL-6, TGF-α and EGF werefound to have significant value in diagnose chronic stress, and MIP-1α had the best effect withan area under ROC of0.882(95%CI:0.720-1.043), p<0.001. The optimal cutoff value was25.06pg/mL and the sensitivity was90%while the specificity was80%. During chronic stress,MIP-1α level was found negatively correlated with hostility score significantly(R=0.45, p=0.01).Conclusion: Chronic social restriction stress can elevate serum cortisol concentration and impacton various cytokine level, it dramatically induced disorder of cytokines secretion. Furthermore,serum MIP-1α level can be served as a potential biomarker for chronic stress.