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 celi 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<0.05 and p<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 contrastM leprae inoculated animals receiving either of these agents showed a significant reduction of granulomatous infiltration at both the inoculation site (p<0.001) and in the primary draining lymph node (p<0001). 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 withM 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. the gastrointestinal tract, of a variety of immune modulating agents acting at varying stages in the immune response. Cyclophosphamide and methotrexate were chosen as their effects on the immune system in the guinea pig have already been extensively investigated.2 3 Hydrocortisone is of interest because prednisolone was the first drug shown by controlled trials4 to be effective in the treatment of Crohn's disease, and, with other glucocorticoids in systemic and topical forms, has remained a mainstay of treatment. Cyclosporin A was studied because of its unique mechanism of action' and its putative role67 as a second line agent in the treatment of refractory or relapsed Crohn's disease. Materials and methods