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

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Abstract
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.