Inhibition of purine nucleoside phosphorylase activity and of T-cell function with allopurinol-riboside.

Allopurinol-riboside competitively inhibits the action of purine nucleoside phosphorylase on inosine in vitro with a Ki of 277 mumol. After simple incubation of allopurinol-riboside with PNP, allopurinol was not formed. Lymphocyte blastogensis induced by PHA and Con A was significantly suppressed by allopurinol-riboside in a concentration-dependent manner. When LPS was used as a mitogen, the inhibition of allopurinol-riboside on lymphocyte proliferation was less marked. Humoral immunity was not suppressed by allopurinol-riboside. In contrast, cellular immunity was significantly suppressed by allopurinol-riboside in vivo. These results suggested that allopurinol-riboside is a drug which produces a model of PNP deficiency, and that it may be a useful inhibitor of cellular immunity.