Susceptibility to adjuvant-induced arthritis among germfree, specific-pathogen-free, and conventional rats

Abstract

Germfree F344 rats developed severe arthritis with 100% incidence after a single intradermal injection of either squalane containing 0.5 mg of heat-killed Mycobacterium bovis BCG or a water-in-oil emulsion containing 0.2 mg of peptidoglycan derived from Staphylococcus epidermidis. Conventional F344 rats developed less-severe arthritis with 20% incidence for heat-killed BCG and 0% incidence for peptidoglycan. Specific-pathogen-free rats showed an intermediate susceptibility between germfree and conventional rats. Interestingly, both unimmunized specific-pathogen-free and conventional rats, but not unimmunized germfree rats, showed weak delayed-type hypersensitivity reactions to peptidoglycans derived from either S. epidermidis or Lactobacillus plantarum, suggesting that a bacterial flora may furnish a stimulus for induction of cell-mediated immunity to ubiquitous bacterial peptidoglycans. It is thus possible that although a bacterial flora is not necessary for development of adjuvant arthritis, it may have some suppressive effect on the development of the disease in specific-pathogen-free and conventional F344 rats, possibly through modulation of the immune response. Adjuvant arthritis (AA) can be induced by a single injection of a water-in-oil emulsion containing mycobacterium (14), many other bacteria, and their cell walls (8, 11). A common factor among these bacterial cell walls responsible for promoting the development of AA was proved to be peptidoglycans (PGs) (12), which are found universally in all bacterial cell walls. This disease has been generally believed to be the result of a delayed-type hypersensitivity (DTH) response to components of bacterial cell walls (20), such as PGs (12). The precise mechanisms which underlie its development are still obscure. There

Diversification of response to hsp65 during the course of autoimmune arthritis is regulatory rather than pathogenic

“…In a preliminary study, we observed that Fisher F344 rats raised in a barrier facility (BF) (BF-Fisher rats) were susceptihle to AA, whereas Fisher rats raised in a conventional (CV) facility (CV-Fisher rats) developed resistance to AA. A similar finding has previously been reported from another laboratory (82). In our study, upon transfer of BF-Fisher rats into a CV facility, these rats acquired resistance to AA within a few weeks.…”

Reverse Effect of Gram‐Positive Bacteria vs. Gram‐Negative Bacteria on Adjuvant‐Induced Arthritis in Germfree Rats

“…To pursue this matter, it seems very important to investigate whether or not germfree rats can develop adjuvant-induced arthritis. Pearson et al (33), and we in our previous paper (19), reported that adjuvant-induced arthritis can be induced in germfree and conventional rats with equal ease and suggested that the bacterial flora is not necessary for development of the disease and rather modulates the development of the disease, since germfree rats developed more severe disease than that in specific pathogen-free and conventional rats.…”

“…The skin thickness was carefully recorded by measuring both ears with a spring-loaded type micrometer (Mitsutoyo Mfg. Co., Tokyo, Japan) at 24 and 48 hr for delayed-type hypersensitivity (9,19,22,25). In some experiments, sections of the ears were stained with hematoxylin and eosin after fixation with 10% formalin.…”

Role of the Bowel Flora for Development of Immunity to hsp 65 and Arthritis in Three Experimental Models

“…The intestinal bacterial flora is known to play a role in modulation of an immune response and in experimental models of arthritis, as adjuvant-or streptococcal cell wall arthritis, disease severity may be modulated by alterations in the bowel flora [1][2][3]. In the human disease rheumatoid arthritis (RA) an involvement of the bowel flora has been suggested in the aetiology, although no conclusive evidence for this is at present available [4].…”