Dual Role of Interleukin-10 in Murine Lyme Disease: Regulation of Arthritis Severity and Host Defense

Autor: Cory Teuscher, Jeanette P. Brown, Janis J. Weis, James F. Zachary, R. Mark Wooten
Rok vydání: 1999
Předmět:
Zdroj: Infection and Immunity. 67:5142-5150
ISSN: 1098-5522
0019-9567
DOI: 10.1128/iai.67.10.5142-5150.1999
Popis: In the murine model of Lyme disease, C3H/He mice exhibit severe arthritis while C57BL/6N mice exhibit mild lesions when infected with Borrelia burgdorferi . Joint tissues from these two strains of mice harbor similar concentrations of B. burgdorferi , suggesting that the difference in disease severity reflects differences in the magnitude of the inflammatory response to B. burgdorferi lipoproteins. Stimulation of bone marrow macrophages from C3H/HeN mice with the B. burgdorferi lipoprotein OspA resulted in higher-level production of the inflammatory mediators tumor necrosis factor alpha, nitric oxide, and interleukin-6 (IL-6) than that of macrophages from C57BL/6N mice. In contrast, macrophages from C57BL/6N mice consistently produced larger amounts of the anti-inflammatory cytokine IL-10 than did C3H/HeN macrophages. Addition of recombinant IL-10 suppressed the production of inflammatory mediators by macrophages from both strains. IL-10 was found to modulate B. burgdorferi -induced inflammation in vivo, since C57BL/6J mice deficient in IL-10 (IL-10 −/− ) developed more severe arthritis than wild-type C57BL/6J mice. The increase in arthritis severity was associated with a 10-fold decrease in the number of B. burgdorferi organisms present in ankle tissues from IL-10 −/− mice. These findings suggest that in C57BL/6 mice, IL-10-dependent regulation of arthritis severity occurs at the expense of effective control of bacterial numbers.
Databáze: OpenAIRE
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