The effect of selected immunomodulating agents on experimental contact reactions

A guinea pig experimental model which allows comparison of the macroscopic appearance of skin tests with the nature and degree of the dermal inflammatory cell infiltrate has been used to study the effects of cyclophosphamide, methotrexate, azathioprine and cyclosporin A on contact reactions. The immunomodulating capabilities of the agents tested are assessed by their effects on the allergic contact reaction to oxazolone, a cell-mediated delayed hypersensitivity reaction. Non-specific, anti-inflammatory actions are assessed by effects on the toxic contact reaction to croton oil. Changes are compared to findings in reference animals for each reaction. The reference materials and the uses and limitations of the experimental model are evaluated. When administered prior to sensitization, all agents enhanced the macroscopic appearance of the allergic contact reactions. Changes in the dermal cellular infiltrates were not pronounced. When administered prior to testing, cyclophosphamide, methotrexate and azathioprine caused changes compared to controls which varied in direction and degree both macroscopically and microscopically. Cyclophosphamide which was the most active agent showed non-specific, anti-inflammatory effects and caused a peripheral blood leukopenia, the level and character of which was essentially independent of the dermal cellular infiltrate of tests. Cyclosporin A demonstrated no non-specific, anti-inflammatory activity on the toxic reaction, but had by far the most pronounced immunosuppressant effect of the agents tested, with virtual quenching of both the macroscopic appearance and all aspects of the dermal cellular infiltrates of the allergic contact reaction.