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

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 ␣ 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 ␣ 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 CFAinduced 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.

Helminth Infections and Host Immune Regulation

“…Thus, the schistosome suppression of arthritis pathology may depend on a lack of egg-induced inflammation, as seen in asthma models of S. mansoni infection (186). The rat tapeworm, Hymenolepis diminuta, also downregulates CFAinduced arthritis in mice in an IL-4R␣-, CD4-, and IL-10-dependent manner, consistent with suppression being due to Th2 induction in these mice (256). Collagen-induced arthritis can also be alleviated by the filarial nematode molecule ES-62 (190).…”

Splenic B Cells fromHymenolepis diminuta–Infected Mice Ameliorate Colitis Independent of T Cells and via Cooperation with Macrophages

“…Knee joint swelling was monitored over a 6d period by an observer blinded to the experimental treatment using mechanical Vernier calipers as described previously (6).…”

Helminthotherapy

“…RA'nın oluşmasına karşı etkin olduğu gösterilen helmintlere örnek olarak S. mansoni, S. japonicum ve H. polygrus'un yanında H. diminuta verilebilir [60,61,63,64] . Bunlardan H. diminuta'nın, CFA aracılı RA'nın indüklemesinden sonra verildiğinde bile, diz şişkinliğini dindirici bir etkisinin olduğu ve iyileşmeyi hızlandırdığı rapor edilmiş-tir [63] .…”