Absence of endogeneous interleukin-10 enhances the evolution of murine type-II collagen-induced arthritis.
Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the immune and inflammatory response. The aim of this study was to investigate the role of endogenous IL-10 in the modulation of the inflammatory response in mice subjected to collagen-induced arthritis. Collagen-induced arthritis (CIA) was induced in mice lacking the gene for IL-10 (IL-10 "knock-out", IL-10KO) and in wild-type control (IL-10WT) mice by an intradermal injection of 100 mul of the emulsion (containing 100 mug of bovine type II collagen) (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. IL-10 wild type (WT) mice developed an erosive, hind paw arthritis when immunised with CII in CFA. Macroscopic clinical evidence of CIA first appeared as peri-articular erythema and oedema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged IL-10WT. The severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. IL-10KO mice experienced higher rates of clinical signs and more severe knee and paw injury as compared to IL-10WT. The degree of oxidative and nitrosative damage was significantly higher in IL-10KO mice than in wild-type littermates, as indicated by elevated malondialdehyde levels and formation of nitrotyrosine and poly (ADP-ribose) synthetase (PARS). Plasma levels of the proinflammatory cytokines, tumour necrosis factor, interleukin-1beta and interleukin-6 were also greatly enhanced in comparison to wild-type mice. These data demonstrate that endogenous IL-10 exerts an anti-inflammatory role during chronic inflammation and tissue damage associated with collagen-induced arthritis, possibly by regulating neutrophil recruitment, and the subsequent cytokine and oxidant generation.
Cuzzocrea
S
S
Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Gazzi, 98100 Messina, Italy. salvator@www.unime.it
Mazzon
E
E
Dugo
L
L
Serraino
I
I
Britti
D
D
De Maio
M
M
Caputi
A P
AP
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000503:physiopathology*; D003094:Collagen / Q000009:adverse effects*; D051546:Cyclooxygenase 2; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003094:Collagen; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases