NDLI: Inflammatory cytokine levels in paw tissues during development of rat collagen-induced arthritis: Effect of FK506, an inhibitor of T cell activation

Content Provider	Springer Nature Link
Author	Magari, K. Miyata, S. Ohkubo, Y. Mutoh, S.
Copyright Year	2004
Abstract	Objective and design: To characterize rat collagen-induced arthritis (CIA) on the basis of levels of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in paw tissues, and further investigate the effect of FK506 (tacrolimus), a potent inhibitor of T cell activation, on cytokine levels.Methods: CIA was induced in female Lewis rats. The volume of hindpaws was measured before and after collagen immunization. TNF-α, IL-1β and IL-6 levels in paw tissue extracts were determined by ELISA. Proteoglycan contents of cartilage in femoral heads was measured as an indication of cartilage destruction. To assess the effect of FK506 on inflammatory cytokine levels, rats were orally treated with 5 mg/kg of FK506 from days 14–21.Results: TNF-α a level in paw tissues did not significantly change compared to levels found before collagen immunization, throughout development of CIA. In contrast, IL-1β and IL-6 levels in paw tissues significantly increased between day 14 and day 28 after collagen imuninization, when the arthritis was at a developed stage. Therapeutic treatment with FK506 reduced the elevated level of IL-6, but not IL-1β, in paw tissue. FK506 treatment was effective in suppressing paw swelling and also recovering the loss of proteoglycan contents in the cartilage.Conclusions: Levels of IL-1β and IL-6, but not TNF-α , in paw tissue were upregulated in association with the development of arthritis in rat CIA. These results suggest that IL-1β and IL-6, rather than TNF-α , may play important roles at local inflammatory sites in producing joint destruction in rat CIA. FK506 may improve arthritis in established stages of CIA, by reducing the elevated level of IL-6.
Starting Page	469
Ending Page	474
Page Count	6
File Format	PDF
ISSN	10233830
Journal	Inflammation Research
Volume Number	53
Issue Number	9
e-ISSN	1420908X
Language	English
Publisher	Birkhäuser-Verlag
Publisher Date	2004-01-01
Publisher Place	Basel
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Immunology Pharmacology/Toxicology Allergology Dermatology Neurology Rheumatology
Content Type	Text
Resource Type	Article
Subject	Pharmacology Immunology

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