INTERLEUKIN-10 SUPPRESSES EXPERIMENTAL CHRONIC, GRANULOMATOUS INFLAMMATION-INDUCED BY BACTERIAL-CELL WALL POLYMERS

Background and Aims-Interleukin 10 (IL10) inhibits monocyte/macrophage and T lymphocyte effector functions, This study examined the effect o f systemically administered IL10 on acute and chronic granulomatous en terocolitis, hepatitis, and arthritis in a rat model. Methods-Lewis ra ts were injected intra-murally with streptococcal peptidoglycan-polysa ccharide (PG-APS) polymers. Beginning 12 hours before PG-APS injection , rats were treated daily with subcutaneous murine recombinant IL10 or vehicle for three or 17 days. Results-IL10 attenuated acute enterocol itis in a dose dependent fashion (p<0 . 01). Protective effects were m ore profound in the chronic granulomatous phase with decreased enteroc olitis and markedly inhibited leucocytosis, hepatic granulomas, and ch ronic erosive arthritis (p<0 . 001). IL10 downregulated tissue IL1, IL 6, tumour necrosis factor alpha, and interferon gamma gene expression, consistent with the in vitro effects of IL10 on PG-APS-stimulated spl enocytes. Caecal IL1 protein concentrations and IL2 and interferon gam ma secretion by in vitro stimulated mesenteric lymph nodes were downre gulated in IL10 treated animals. Conclusions-These results indicate th at exogenous IL10 can inhibit experimental granulomatous inflammatory responses and suggest that IL10 treatment could be an effective new th erapeutic approach in human disorders such as Crohn's disease, rheumat oid arthritis, and sarcoidosis.