Suppression of antigen‐induced arthritis in lewis rats by oral administration of type ii collagen

Abstract

Objective. To assess the effect of orally administered type I1 collagen (CII) in antigen-induced arthritis (AIA).Methods. Arthritis was induced in Lewis rats by immunization with methylated bovine serum albumin (mBSA) in Freund's complete adjuvant, followed by an intraarticular injection of mBSA 2 weeks later. Different doses of CII, mBSA, and an unrelated control protein, keyhole limpet hemocyanin (KLH), were orally administered 5 times over several days prior to the induction of arthritis. Ankle joint swelling and delayed-type hypersensitivity (DTH) responses were measured.Results. Joint swelling was significantly reduced at a dose of 3 p g and 30 p g of CII, but not at 300 pg. The most prominent suppression of AIA was observed when rats were fed 10 mg of mBSA, whereas oral KLH had no effect. DTH responses were significantly reduced in the mBSA-fed rats, but not in rats that were fed CII or KLH.Conclusion. Oral CII can suppress arthritis in an animal model in which immunity to collagen does not play a role. The effect is dose dependent and occurs at lower doses of CII. These results demonstrate the biologic relevance of bystander suppression associated with oral tolerance, and the potential use of this approach to treat human inflammatory joint disease.

LEW.1WR1 Rats Develop Autoimmune Diabetes Spontaneously and in Response to Environmental Perturbation

“…In this regard, they are similar to BBDR rats (25,42,43) and the parental LEW rat (26), which are comparably susceptible. Rheumatoid arthritis occasionally occurs in patients and families with type 1 diabetes (44), and genetic analyses in both the rat and human suggest that some susceptibility loci for both diseases are in linkage disequilibrium (45,46).…”

“…Collagen arthritis. Type 1 diabetes often occurs together with other autoimmune disorders, and both BBDR (25) and standard LEW (26) rats are susceptible to collagen-induced arthritis. As shown in Table 3, LEW.1WR1 rats are also highly susceptible to this disorder.…”

Chicken type II collagen induced immune balance of main subtype of helper T cells in mesenteric lymph node lymphocytes in rats with collagen-induced arthritis

“…Beginning with CIA in rats [14] and mice [15], oral administration of CII has been found to suppress virtually all experimentally inducible animal models for RA [16][17][18][19]. Histopathological studies Fig.…”

“…5 Effects of CCII on the activity of IL-2 from MLN lymphocytes in CIA rats. CIA rats were treated with CCII for 7days (days [14][15][16][17][18][19][20][21]. IL-2 activity from MLN lymphocyte supernatant was measured by ConA-induced splenocyte proliferation in C57BL/6J mice.…”

Bystander suppression of occupational hapten sensitization in rats made tolerant to ovalbumin

“…Such production of antigen nonspecific suppressive cytokines can also result in diminished responses to an unrelated antigen in the close vicinity, known as bystander suppression [12]. Bystander suppression has been demonstrated in several autoimmune disease models, including suppression of experimental allergic encephalomyelitis by feeding myelin basic protein [11,13] or ovalbumin [12], suppression of antigen-induced arthritis by type II collagen [14,15] and suppression of virus-induced diabetes by insulin [16]. In a rat model of focal cerebral ischaemia, tolerance to myelin basic protein decreased stroke size [17].…”