Exacerbated fatigue and motor deficits in interleukin-10-deficient mice after peripheral immune stimulation.
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-1beta, IL-6, and TNFalpha 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-1beta 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 TNFalpha 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.
Krzyszton
C P
CP
Integrative Immunology and Behavior Program, University of Illinois, Urbana, Illinois 61801, USA.
Sparkman
N L
NL
Grant
R W
RW
Buchanan
J B
JB
Broussard
S R
SR
Woods
J
J
Johnson
R W
RW
D000367:Age Factors; D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005080:Exercise Test; D005221:Fatigue / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009044:Motor Cortex / Q000378:metabolism; D011596:Psychomotor Disorders / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D016753:Interleukin-10