The selectivity of isoprinosine, NPT 15392, avridine and cyclophosphamide on multiple immune responses in rats

Multiple concomitant immune responses were assessed in individual rats following treatment with the immunoenhancing drugs, isoprinosine (5 or 50 mg/kg), NPT 15392 (0.1 or 1.0 mg/kg) and avridine (1 or 25 mg/kg), or the immunosuppressant, cyclophosphamide (75 mg/kg). Immune responses assessed in each rat were specific antibody synthesis, delayed-type hypersensitivity (DTH), natural killer cell (NKC) cytotoxicity and production of three immunoregulatory cytokines, interleukin 1 (IL1), interleukin 2 (IL2) and prostaglandin E2 (PGE2). Spleen and thymus weights and numbers of splenocytes and resident peritoneal cells were also recorded. Rats treated with isoprinosine had dose-related, significant increases in spleen weights and DTH reactions. Rats treated with NPT 15392 had significantly enhanced DTH reactions at the 0.1 mg/kg dose. Rats treated with the 25 mg/kg dose of avridine had significantly increased spleen weights, DTH reactions and NKC cytotoxicity. The effect of avridine treatment on DTH reactions and IL1 and IL2 production was inverse to the dose administered, while the NKC response was directly related to the dose. Thymus weights, antibody production and PGE2 synthesis were not significantly altered in rats treated with isoprinosine, NPT 15392 or avridine. Cyclophosphamide-treated rats had significantly reduced spleen and thymus weights, antibody synthesis, DTH reactions, NKC cytotoxicity and IL2 production, but IL1 and PGE2 synthesis were significantly elevated. It can be concluded that isoprinosine, NPT 15392 and avridine act as general immunostimulants in the rat, with avridine having the greatest effect under these experimental conditions. It also appears that these drugs are differentially immunoselective in the rat and this effect is at least partially related to the dose administered. These results could be of significance in the selective therapeutic manipulation of different arms of the immune system. Also, enhanced production of PGE2 following cyclophosphamide treatment may contribute to the immunosuppressive effects of this drug.