The effect of azathioprine on cell-mediated immunity (CMI) to Candida albicans in Crohn's disease

Abstract

Using as antigen a suspension of Candida albicans, strain A, three tests of cell-mediated immune reactivity (delayed skin hypersensitivity, lymphocyte stimulation and leucocyte migration inhibition) were undertaken in patients with Crohn's disease to determine the effect of azathioprine given as the sole anti-inflammatory medication. No significant effect was demonstrable on 48 hr induration in the skin test. Uptake of thymidine by lymphocytes in vitro, whether spontaneous or antigenically induced, was greater during azathioprine treatment than before it. The assumption that this finding might be associated with clinical recovery was confirmed in antigen-stimulated cultures by the fact that, irrespective of treatment, patients who had been able to resume their normal occupations showed markedly higher reactivity than those who were still disabled (P<0·002). It was also found that azathioprine treatment in itself potentiated lymphocyte stimulation by C. albicans. The range of values for inhibition of leucocyte migration was the same in the treated and untreated groups, but certain individuals displayed a substantial change in reactivity when re-tested after institution or discontinuation of azathioprine treatment. Untreated patients with Crohn's disease did not differ from normal subjects in their cell-mediated reactivity to C. albicans. The increased rate of thymidine uptake by lymphocytes from patients receiving azathioprine is discussed in the light of recent hypotheses linking virus-induced malignancy with lymphoblastic transformation.