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

C. P. Krzyszton, N. L. Sparkman, R. W. Grant, J. B. Buchanan, S. R. Broussard, J. Woods, R. W. Johnson

Research output: Contribution to journalArticlepeer-review

Abstract

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 TNFα 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 TNFα 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.

Original languageEnglish (US)
Pages (from-to)R1109-R1114
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume295
Issue number4
DOIs
StatePublished - Oct 2008

Keywords

  • Brain
  • Lipopolysaccharide
  • Motor coordination
  • Proinflammatory cytokines

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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