INHIBITION OF HUMAN MIXED LYMPHOCYTE REACTIONS BY SERA AND URINE DIALYSATES FROM NIRIDAZOLE-TREATED RATS

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Abstract
Sera and urine dialysates from niridazole-treated rats were potent inhibitors of the human mixed lymphocyte reaction (MLR). Niridazole itself at low concentrations failed to inhibit the in vitro reaction, indicating that metabolites of niridazole were immunosuppressive, rather than the parent compound. The percentage of MLR inhibition was directly related to the dose of niridazole given and increased with the number of treatments administered. Inhibitory factors were present in rat sera collected up to 4 days after the last of 3 doses of niridazole but gradually disappeared over the next 3 days. The percentage of MLR inhibition was directly related to the concentration of pooled niridazole serum and niridazole urine dialysate (NUD) included in the MLR culture, and the latter was the more potent source of active metabolites. MLR were completely suppressed when NUD (10% vol/vol) was added before or 30 min after mixing allogeneic cells, but at 3 h and subsequently, no inhibition occurred. The active factor apparently interfered with events occurring early in the antigen recognition phase of the MLR. Pretreatment of responder or stimulator lymphocytes with NUD suppressed subsequent MLR stimulation, suggesting that the active factor was absorbed nonspecifically onto lymphocytes and prevented interactions at the surface membrane. Vigorous washing of NUD-blocked lymphocytes did not restore MLR reactivity, although the washing from this procedure did contain an agent able to inhibit the MLR. Since niridazole metabolites inhibit in vitro sensitization to alloantigens, a clinical use for this agent in preventing allograft rejection is suggested.

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