Azathioprine suppresses the mixed lymphocyte reaction of patients with Lesch‐Nyhan syndrome.

Abstract

The mixed lymphocyte reaction of Lesch‐Nyhan patients (HGPRT deficient) was used to study the immunosuppressive effects of azathioprine and 6‐ mercaptopurine (6‐MP). Mitogen stimulated lymphocytes of these patients are highly resistant to azathioprine and 6‐MP. When both stimulator and responder lymphocytes in the MLR were HGPRT deficient, azathioprine (36 microM) was much more inhibitory than 6‐MP (100 microM). Azathioprine produced inhibition of 98.2% and 78.5% compared with the values of 63.9% and 30.6% for 6‐MP. The difference in inhibitory activity between azathioprine and 6‐MP was reduced when normal stimulator lymphocytes were cultured with HGPRT deficient responder lymphocytes in the MLR. These results provide very strong evidence that the nucleotide metabolites of azathioprine and 6‐MP are unnecessary for immunosuppression. They also suggest that azathioprine and 6‐MP interfere with antigenic triggering of the MLR. 1985 The British Pharmacological Society