Running Head : IL - 10 and motor deficits 1 2 3 4 Exacerbated fatigue and motor deficits in interleukin - 10 deficient 5 mice after peripheral immune stimulation

24 The anti-inflammatory cytokine interleukin (IL)-10 is important for regulating 25 inflammation both in the periphery and brain but whether it protects against infectionor age26 related psychomotor disturbances and fatigue is unknown. Therefore, the current study 27 evaluated motor coordination, time to fatigue, and several central and peripheral 28 proinflammatory cytokines in male young adult (3 mo) and middle-aged (12 mo) wild type (IL29 10) and IL-10 deficient (IL-10) mice after i.p. injection of lipopolysaccharide (LPS) or 30 saline. No differences were observed due to age so data from the two ages were pooled and 31 analyzed to determine effects of genotype and treatment. Treatment with LPS increased IL-1β, 32 IL-6, and tumor necrosis factor α (TNFα) mRNA in all brain areas examined in both IL-10 33 and IL-10 mice but to a greater extent and for a longer time in IL-10 mice. Plasma IL-1β and 34 IL-6 were increased similarly in IL-10 and IL-10 mice 4 h after LPS but remained elevated 35 longer in IL-10 mice; whereas TNFα was higher in LPS-treated IL-10 mice throughout. LPS 36 treatment did not affect motor performance or motor learning in IL-10 mice; however, both 37 were reduced in LPS-treated IL-10 mice compared to saline. Furthermore, although LPS 38 reduced the time to fatigue in both IL-10 and IL-10 mice, the effects were exacerbated in IL39 10mice. Thus, the increased brain and peripheral inflammation induced by LPS in IL-10 40 mice was associated with increased coordination deficits and fatigue. These data suggest that IL41 10 may inhibit motor deficits and fatigue associated with peripheral infections via its anti42 inflammatory effects. 43