A pathogenetic model for erosive synovitis. Lessons from animal arthritides

Postdysenteric Reiter's syndrome and the arthritis associated with jejunal bypass surgery for obesity L Aggest that the gastrointestinal tract is a possible source of bacterial products capable of initiating chronic inflammatory arthritis. Lactobacillus casei, a common component of the enteric flora, has a cell wall structure similar to that of arthritogenic streptococci. In this study we have demonstrated that a single intraperitonea1 injection of an aqueous suspension of the cell walls of Lactobacillus casei induces a dose-dependent, chronic, symmetric, erosive, peripheral polyarthritis in inbred LEW/N female rats. This model suggests that bacteria in the "normal enteric flora'' may be a source of inflammatory products capable of inducing chronic erosive polyarthritis.The arthritides associated with postdysenteric Reiter's syndrome and jejunal bypass surgery for obesity have focused attention on the gastrointestinal tract as a source of bacterial products which might induce chronic arthritis (1-4). None of the enteric flora, however, has previously been demonstrated to be arthritogenic in experimental animals unless administered with mineral oil (5). Lactobacillus casei is a gram-positive, facultative. anaerobic bacterium commonly found in the oral, vaginal, and gastrointestinal Submitted for publication March 3, 1983: accepted in flora of both rats and humans (6). We have chosen to study L casei because its cell wall possesses similarities to the cell wall of the Group A streptococcus (6). Previous investigations have shown that the systemic injection of an aqueous suspension of Group A streptococcal cell wall fragments induces chronic, erosive polyarthritis in selected inbred rat strains (7,8).In the present study we examined the arthritogenic potential of an aqueous suspension of nonviable whole cell or cell wall fragments from L casei strain 1 1578 from the American type culture collection (ATCC 115781, which was originally isolated from normal human oral flora (9). We used the LEW/N female rat in this model because of its previously documented susceptibility to streptococcal cell wallinduced arthritis (8). Our findings clearly demonstrate that a single intraperitoneal injection of the cell wall of L casei in aqueous suspension is capable of inducing a chronic inflammatory polyarthritis of the distal joints. Whole cell fragments of L casei were prepared from 5 gm packed wet weight of bacteria sonicated in 20 ml of PBS for 120 minutes at 4°C at maximum frequency using a Biosonic IV sonicator fitted with a $-inch probe (VWR Scientific, Baltimore, MD). Cell wall fragments Here isolated in the MATERIALS AND METHODS

Section: Discussionmentioning

confidence: 99%

Polyarthritis in rats following the systemic injection of lactobacillus casei cell walls in aqueous suspension

Lehman

Allen

Plötz

et al. 1983

“…A variety of rat models of polyarthritis (15)(16)(17) has been described, but the relevancy of these animal models to the human disease is not clear. A major criticism of these models has been that the inciting antigen is foreign in nature and is usually of bacterial origin.…”

Section: Discussionmentioning

confidence: 99%

STUDIES ON TYPE II COLLAGEN–INDUCED POLYARTHRITIS IN RATS. Effect of Antiinflammatory and Antirheumatic Agents

Sloboda¹,

Birnbaum²,

Oronsky³

et al. 1981

The effect of a variety of antiinflammatory and antirheumatic agents on both developing and established lesions of type I1 collagen induced polyarthritis in rats was examined. Administration of the nonsteroidal antiinflammatory agents indomethacin or phenylbutazone suppressed the paw inflammation associated with the disease without affecting type I1 collagen antibody titers. Radiographic analysis of the joints showed suppression of several parameters related to joint destruction. This was most probably related to the antiinflammatory properties of the two drugs. Administration of prednisolone, a steroidal antiinflammatory agent, suppressed paw inflammation; type 11 collagen antibody titers were significantly decreased in the developing lesion, but the drug had no effect on antibody titers in the established lesion. Radiographic analysis of the joints showed decreases in several parameters of joint destruction. Cyclophosphamide, an immunosuppressive agent, completely suppressed the inflammation associated with the developing lesion but had only minimal effect against the established disease. Collagen antibody titers were decreased and an improvement in only one radiologic parameter (periostitis) was detected. Treatment with antirheumatic agents such as gold thioglucose or levamisole enhanced severity of inflam- Submitted for publication April 30, 1980; accepted in revised form October 7, 1980. mation in the established lesion and caused increases in collagen antibody titers. Radiographic analysis of the joints indicated that while gold had no effect, levamisole enhanced joint destruction. Treatment with D-penicillamine had no effect on paw inflammation, despite increases in collagen antibody titers. Radiographic analysis of the joints indicated an improvement in all parameters related to joint destruction in animals treated with penicillamine.The demonstration of antibodies to collagen in the sera and synovial fluids of patients with rheumatoid arthritis (1-8) has led to the view that immunologic hypersensitivity to collagen may, at least in part, contribute to the inflammation and joint destruction that is observed in the disease. Supporting this view, several studies (9;13) have shown that when native cartilage specific type I1 collagen (homologous or heterologous) in an oil emulsion was injected intradermally into rats, approximately 40% of the animals developed an inflammatory polyarthritis. Denatured type I1 collagen or the other genetically distinct forms such as type I, 111, and IV did not elicit this response. Passive transfer of the polyarthritis in rats was also achieved by the administration of sensitized lymph node and spleen cells, again suggesting that the polyarthritis observed in these animals was related, at least in part, to immunologic hypersensitivity to type I1 collagen (14).Although the relationship of this animal model to human disease is not established, several similarities exist between the two lesions. Both lesions contain mononuclear cell infiltrates in the synovial tissue and begin...

“…These possibilities exist whether or not one introduces the concept of persistent, nonbiodegradable antigens (36). Recent elegant work, showing chronic However, because of the similarities among all of the bacterial peptidoglycans, these experiments should be repeated in germ-free animals to rule out other sources of continued antigenic supply.…”

Section: Capsule Outer Membranementioning

confidence: 99%

The infectious etiology of rheumatoid arthritis.

Bennett

1978

Several possible mechanisms of chronic inflammatory arthritis that might be initiated by infectious agents are discussed. Some recent information on mycoplasma infections, long-term virus infections, and shed bacterial components provides the bases for new experimental approaches. Currently, evidence of involvement of mycoplasma or viral agents in rheumatoid arthritis is tenuous. Chronic peptidoglycan-immunecomplex formation is a consideration that has been discussed, but only recently pursued in depth. It may well be that experimental studies on the infectious etiology of rheumatoid arthritis will be revitalized through an appreciation of the bacterial antigen load in the gastrointestinal tract. The experimental vehicles for testing this possibility are available and should be directly applicable at the clinical level.Throughout the history of rheumatic diseases no possible basis for pathogenesis has been more discussed or pursued, and proved more disappointing, than that of infection. Work in the fields of bacteriology, virology, From the University of Alabama in Birmingham.