Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice

Abstract:

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.

 

Source: Sheng WS, Hu S, Lamkin A, Peterson PK, Chao CC. Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice. Clin Immunol Immunopathol. 1996 Nov;81(2):161-7. http://www.ncbi.nlm.nih.gov/pubmed/8906747

 

Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins.

Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed.

In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed.

The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS.

 

Source: Chao CC1, Janoff EN, Hu SX, Thomas K, Gallagher M, Tsang M, Peterson PK. Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. Cytokine. 1991 Jul;3(4):292-8. http://www.ncbi.nlm.nih.gov/pubmed/1873478