Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice.
Proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha have been proposed to play a role in the pathogenesis of fatigue. In the present study we compared the susceptibility of two mouse strains to immunologically induced fatigue. Daily running of two strains of mice, Balb/c and C57BL/ 6, was assessed after a single injection of Corynebacterium parvum antigen (2 mg/mouse). Spontaneous running activity of each animal was compared to mean running distance prior to injection. To evaluate the involvement of cytokines in fatigue development, C57BL/6 mice were treated with antibodies to specific cytokines at the time of challenge with C. parvum antigen. Also, cytokine mRNA expression was analyzed in the brains of mice at different time periods after immunologic challenge. A significant difference in running activity between the two mice strains was observed after C. parvum antigen inoculation: C57BL/6 mice showing a greater (P < 0.05) reduction in running activity (relative to preinjection levels) and slower recovery to baseline than Balb/c mice. Injection of antibodies specific to either IL-1beta or TNF-alpha did not alter immunologically induced fatigue, suggesting a lack of involvement of these cytokines produced outside of the central nervous system (CNS). However, increased TNF-alpha and IL-1beta mRNA expression was found in the brains of C57BL/6 compared to that seen in Balb/c mice at 6, 10, and 15 days after C. parvum antigen injection. The elevated CNS cytokine mRNA expression corresponded to development of fatigue. These findings are consistent with the hypothesis that expression of proinflammatory cytokines within the CNS plays a role in the pathogenesis of immunologically mediated fatigue.
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, and the University of Minnesota Medical School, 55404, USA.
W S
WS
Sheng
S
S
Hu
A
A
Lamkin
P K
PK
Peterson
C C
CC
Chao
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000494:pharmacology; D001923:Brain Chemistry; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D004198:Disease Susceptibility; D015673:Fatigue Syndrome, Chronic / Q000276:immunology*; D005260:Female; D007375:Interleukin-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology*; D008810:Mice, Inbred C57BL / Q000276:immunology*; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009043:Motor Activity / Q000276:immunology / Q000502:physiology; D011425:Propionibacterium acnes / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000906:Antibodies; D000942:Antigens, Bacterial; D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha