Observations on the Kveim reaction using an animal model of granulomatous bowel disease.

Striking differences were observed between the visceral and cutaneous responses after tests with validated Kveim and normal spleen suspensions in a guinea pig model of granulomatous bowel disease. Five of six animals sensitised with BCG showed positive responses at the ileal Kveim test site whereas all six had negative cutaneous Kveim tests. Conversely, two of six animals sensitised with irradiated Mycobacterium leprae showed positive cutaneous Kveim tests and only one a positive response in the ascending colon. All six showed negative responses at the ileal Kveim test site. No positive visceral or cutaneous responses were observed in either group of animals after tests with normal spleen suspension. These findings are discussed in relation to the positive Kveim responses previously reported among patients with Crohn's disease, tuberculoid and lepromatous leprosy, and among seemingly healthy BCG vaccinated subjects. The findings provide further evidence in support of a possible mycobacterial aetiology for sarcoidosis and Crohn's disease.

Effect of the immune modulating agents cyclophosphamide, methotrexate, hydrocortisone, and cyclosporin A on an animal model of granulomatous bowel disease.

This study was undertaken to determine the effect of cyclophosphamide, methotrexate, hydrocortisone, and cyclosporin A on a model of granulomatous infiltration in the terminal ileum and draining lymph nodes of the guinea pig. Treatment groups of six animals were used and compared to untreated groups of 12. Epithelioid cell granulomas and primary macrophage granulomas were induced by the inoculation of BCG (Pasteur) and irradiated Mycobacterium leprae respectively into the terminal ileum of the guinea pig. The response to purified protein derivative of tuberculin was reduced in both groups of animals receiving any of these agents. Cyclophosphamide and methotrexate treated animals inoculated with BCG or M leprae showed a significant reduction of granulomatous infiltration at the inoculation site (p less than 0.05 and p less than 0.001 respectively). BCG inoculated animals treated with either hydrocortisone or cyclosporin A showed no reduction in granulomatous infiltration at either the inoculation site or the draining lymph nodes. By contrast M leprae inoculated animals receiving either of these agents showed a significant reduction of granulomatous infiltration at both the inoculation site (p less than 0.001) and in the primary draining lymph node (p less than 0.001). Ziehl Neelsen staining showed an increased proportion of animals with detectable acid fast bacilli (AFB) at the inoculation site in the groups receiving hydrocortisone (50%) and methotrexate (67%) compared to untreated controls (8%). No AFB were observed in any of the animals inoculated with M leprae. In conclusion, this model may be helpful in elucidating the mechanism of T lymphocyte response in Crohn's disease and the variable clinical response seen with the use of immunosuppressive agents in this condition.

An experimental animal model of granulomatous bowel disease.

A study has been undertaken of the granulomatous response induced in the ascending colon and terminal ileum of the guinea pig by the direct inoculation of mycobacterial antigens. Live BCG (Pasteur) 2 x 10(7) at two weeks induced epithelioid cell granulomas in both large and small bowel and in the draining lymph nodes. The area of infiltration was significantly greater for a given inoculum in the large bowel. Acid fast bacilli were present on Ziehl Neelson stained sections of the large bowel infiltrate, but only rarely in sections from the small bowel lesions. The response to skin testing with a standardised amount of purified protein derivative was less in animals inoculated in the small bowel. Inoculation with 2 x 10(9) cobalt irradiated BCG gave rise, at five weeks, to granulomas containing lesser numbers of epithelioid cells and caseation was sometimes evident. There was a similar but smaller difference in the degree of infiltration at the two inoculation sites. Ziehl Neelson staining failed to reveal the presence of acid fast bacilli in any sections of the bowel infiltrates. Skin testing with purified protein derivative gave a response which was greater in animals inoculated in the small bowel. An identical dose of Cobalt irradiated M leprae induced at five weeks a predominantly macrophage granuloma in both the large and small bowel, with no significant difference in the degree of infiltration at the two sites. No acid fast bacilli were seen in Ziehl Neelson stained sections of the bowel and skin testing with purified protein derivative was reduced. These findings and their relevance to studies of the aetiology of Crohn's disease are discussed.