High-density proteoglycan induces specific suppression of adjuvant-induced arthritis in rats

Abstract

SUMMARYIn vitro data support the view that T cells in adjuvant-induced arthritis (AIA) respond lo the proteoglycan (PG) component of articular cartilage; however, an in vivo role for PG in AIA has yet lo be shown. To do so. we examined the effects of pretreatmcnt with bovine cartilage high density PG (HDPG) on AIA induced by heat-killed Mycobacierium butyricum in Lewis rats. Purified bovine cartilage HDPG emulsified in Frcund's incomplete adjuvant (FIA) was injected intradermally into rats 7 days before challenge with Myco. butyricum. The severity of arthritis was significantly suppressed in rats prctreated with as little as 0-75 mg of HDPG. and Ihe arthritis was completely suppressed in rats pretreated with 30 mg of HDPG. This suppression was specific, as the same treatment did not protect against type 11 collagen-induced arthritis. Suppression of AIA is primarily a property o\' the HDPG, as suppression of the arthritis was significantly less wiih pretreatment with 30 mg of middle density fractions of PG, and no suppression was observed with pretreatment with the lowest density fraction of PG. Thus we report that pretreatment with cartilage HDPG. but not lower density PG.can induce specific suppression of AIA. These in vivo results support the view thai immunity to cartilage HDPG plays a major role in the pathogenesis of AIA, and can induce specific tolerance to ihis type of arlhritis.