The effect of some immunomodulating agents on the sensitization phase of experimental contact allergic reactions.

In an experimental model which allows comparison of the macroscopic changes with the differentiated dermal inflammatory cell infiltrate of the allergic contact reaction to oxazolone in guinea pigs, the effects of single doses of the cytostatic agents cyclophosphamide, methotrexate and azathioprine and the anti-lymphocyte agent cyclosporin A administered prior to sensitization were studied. All the agents tested increased the degree of erythema and edema of reactions compared to controls. The dermal inflammatory mononuclear cell response showed little significant increase and would not seem to explain the enhancement of reactions. The number of basophils in reactions was not significantly different from controls, and there is no evidence for early arrival, degranulation and destruction of basophils prior to our first routine assessment at 24 h. The number of mast cells in the reactions was also unchanged. A role for the latter two cells involving degranulation without changes in the number of cells could provide a possible explanation for the augmentation of the vascular response. A mechanism for the effect of cyclophosphamide other than T-suppressor lymphocyte susceptibility based on selective cytostatic effects on precursor cells may need to be considered.