Cytokines in the brain, induced by various inflammatory challenges have been linked to sickness behaviors, including fatigue. However, the brain cytokine response to exercise is not well understood. Preliminary data show that exaggerated fatigue following downhill vs uphill running is associated with increased brain IL-1b concentration. PURPOSE This study more specifically determined the role of brain IL-1b in this model using intracerebroventricular (ICV) injections of IL-b or IL-1b receptor antagonist (IL-1bra) in uphill and downhill runners, respectively. Methods 64 male C57BL/6 mice were assigned to 1 of 4 groups (UP-IL-1b, DWN-SAL & DWN-IL-Ira). Mice were initially run at 22 m/min and −14% or +14% grade, for 150-min. Fatigue was assessed 12–24hr later via voluntary wheel running (Exp.1) or treadmill running to fatigie) Exp. 2). In Exp 1, 8-hr after the initial run, UP runners received ICV injections of IL-1b (900pg/mouse in 2μ saline) or saline (2 μL), whereas DWN runners received IL-1ra (1.8μ/mouse in 2 μ saline) or saline (2 μL). Then, 2-hr later, all 4 groups were monitored for 24-hr voluntary wheel running patterns. In Exp.2, the protocol was identical except that injections were given 22-hr after the initial run and fatigue was assessed 2-hr later using a treadmill run time to fatigue test. RESULTS In Exp.1, injection of IL-1b in uphill runners decreased wheel running (distance, time and peak speed during the subsequent two 12-hr active cycles (lights out) vs. saline injected mice, and IL-1ra improved wheel running in Downhill runners vs. saline mice. In Exp.2, IL-1b injection decreased run-times to fatigue in the uphill group, and IL-1ra increased run time. CONCLUSION These results support the hypothesis that increased brain IL-1b plays an important role in fatigue following muscle-damaging exercise and perhaps other inflammatory challenges.
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