Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of pro-inflammatory mediators.
Various experimental and epidemiological studies have demonstrated that helminth infections affect outcomes of allergic or autoimmune disorders. Here, we examined the effects of Schistosoma mansoni infection on mouse collagen-induced arthritis, one of the most widely used animal models for rheumatoid arthritis. Male DBA/1 mice were infected with S. mansoni 2 weeks prior to being immunized with type II collagen (IIC). Cytokine mRNA expression in mouse paws, cytokine production by ConA-stimulated spleen cells, and anti-IIC antibodies were evaluated in addition to the severity of arthritis. S. mansoni infection significantly reduced the severity of arthritis. Anti-IIC IgG and IgG2a levels were lower in infected than uninfected mice. With regard to cytokine producing potentials in the infected mice, the down-regulation of Th1 (IFNgamma) and pro-inflammatory cytokines (TNFalpha and IL-17A), and up-regulation of Th2 (IL-4) and an anti-inflammatory cytokine (IL-10) were observed.In addition, real-time PCR revealed that the augmentation of pro-inflammatory mediators such as IL-1 beta, IL-6 and receptor activator of NFkappaB ligand in inflamed paws was abrogated by S. mansoni infection [corrected]. In conclusion, schistosome infection reduced the severity of autoimmune arthritis via systemic and local suppression of pro-inflammatory mediators, suggesting the potential of parasite-derived materials as therapeutic agents against rheumatoid arthritis.
Department of Immunology and Parasitology, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan. yosada@med.uoeh-u.ac.jp
Yoshio
Y
Osada
Shoichi
S
Shimizu
Takashi
T
Kumagai
Sohsuke
S
Yamada
Tamotsu
T
Kanazawa
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D024043:Collagen Type II / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D007074:Immunoglobulin G / Q000032:analysis; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000032:analysis; D007378:Interleukins / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D024043:Collagen Type II; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D007378:Interleukins; D012333:RNA, Messenger; C048844:anti-IgG; D007371:Interferon-gamma