Infection with an intestinal helminth parasite reduces Freund's complete adjuvant–induced monoarthritis in mice

Authors


Abstract

Objective

Assessment of infection with helminth parasites in murine models of disease could identify antiinflammatory mechanisms that translate into treatments for arthritic disease. The aim of this study was to test the ability of infection with the tapeworm Hymenolepis diminuta to ameliorate Freund's complete adjuvant (CFA)–induced monoarthritis in mice.

Methods

Mice received CFA with or without H diminuta, and knee swelling, pain, and measures of inflammation were assessed.

Results

Injection of CFA resulted in rapid (within 24 hours) and sustained (lasting 20 days) knee swelling, a decreased pain threshold, increased blood flow to the knee, and increased production of tumor necrosis factor α and interleukin-12p40 (IL-12p40). In mice that were infected with H diminuta 8 days prior to receiving CFA, the severity of arthritis was reduced as assessed by these indices of inflammation and infection 2 days after CFA injection and resulted in more rapid resolution of knee swelling. This antiarthritic effect required a viable infection and was dependent on adaptive immunity, because infection with H diminuta did not protect mice lacking T cells and B cells or the IL-4 receptor α chain from CFA-induced inflammation. Interleukin-10 was of prime importance in the antiarthritic effect, because IL-10–knockout mice were not protected by infection, the antiarthritic effect was ablated by use of neutralizing IL-10 antibodies, and transfer of CD4+ cells from infected wild-type mice but not IL-10–knockout mice significantly reduced CFA-induced knee swelling.

Conclusion

In mice, the adaptive immune response to infection with H diminuta involves mobilization of IL-10, which has the concomitant advantage of dampening the innate immune responses that drive CFA-induced joint inflammation.

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