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Am J Physiol Regul Integr Comp Physiol 295: R1109-R1114, 2008. First published July 23, 2008; doi:10.1152/ajpregu.90302.2008
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INFLAMMATION, CYTOKINES, NEUROIMMUNE INTERACTIONS

Exacerbated fatigue and motor deficits in interleukin-10-deficient mice after peripheral immune stimulation

C. P. Krzyszton,1,2 N. L. Sparkman,1,2 R. W. Grant,1,3 J. B. Buchanan,1,2 S. R. Broussard,1,2 J. Woods,1,3 and R. W. Johnson1,2

1Integrative Immunology and Behavior Program and Departments of 2Animal Sciences and 3Kinesiology and Community Health, University of Illinois, Urbana, Illinois

Submitted 20 March 2008 ; accepted in final form 20 July 2008

The anti-inflammatory cytokine interleukin (IL)-10 is important for regulating inflammation in the periphery and brain, but whether it protects against infection- or age-related psychomotor disturbances and fatigue is unknown. Therefore, the present study evaluated motor coordination, time to fatigue, and several central and peripheral proinflammatory cytokines in male young adult (3-mo-old) and middle-aged (12-mo-old) wild-type (IL-10+/+) and IL-10-deficient (IL-10–/–) mice after intraperitoneal injection of lipopolysaccharide (LPS) or saline. No age-related differences were observed; therefore, data from the two ages were pooled and analyzed to determine effects of genotype and treatment. LPS treatment increased IL-1β, IL-6, and TNF{alpha} mRNA in all brain areas examined in IL-10+/+ and IL-10–/– mice, but to a greater extent and for a longer time in IL-10–/– mice. Plasma IL-1β and IL-6 were increased similarly in IL-10+/+ and IL-10–/– mice 4 h after LPS but remained elevated longer in IL-10–/– mice, whereas TNF{alpha} was higher in IL-10–/– mice throughout after LPS treatment. Motor performance and motor learning in IL-10+/+ mice were not affected by LPS treatment; however, both were reduced in IL-10–/– mice treated with LPS compared with those treated with saline. Furthermore, although LPS reduced the time to fatigue in IL-10+/+ and IL-10–/– mice, the effects were exacerbated in IL-10–/– mice. Thus the increased brain and peripheral inflammation induced by LPS in IL-10–/– mice was associated with increased coordination deficits and fatigue. These data suggest that IL-10 may inhibit motor deficits and fatigue associated with peripheral infections via its anti-inflammatory effects.

brain; proinflammatory cytokines; motor coordination; lipopolysaccharide



Address for reprint requests and other correspondence: R. W. Johnson, 4 Animal Sciences Laboratory, 1207 W. Gregory Dr., University of Illinois at Urbana Champaign, Urbana, IL 61801 (e-mail: rwjohn{at}illinois.edu)







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