THERAPEUTIC EFFICACY OF RECOMBINANT INTERLEUKIN-6 (IL-6) ALONE AND COMBINED WITH RECOMBINANT HUMAN IL-3 IN A NONHUMAN PRIMATE MODEL OF HIGH-DOSE, SUBLETHAL RADIATION-INDUCED MARROW APLASIA

Using a nonhuman-primate model of radiation-induced bone marrow aplasi a, we examined whether the single, concomitant, or sequential administ ration of recombinant human interleukin-3 (IL-3) and IL-6 would promot e bone marrow regeneration measured by an increase in circulating plat elets (PLT) and neutrophils (PMN). Rhesus monkeys were irradiated at 4 50 cGy and were randomly assigned to one of five treatment protocols, receiving IL-6; IL-3; combined IL-6 and IL-3; sequential IL-3 and IL-6 ; or human serum albumin (HSA) as a control. Cytokines or HSA were adm inistered at total dosages of 15 mu g/kg/day. Complete blood counts an d white blood cell differentials were monitored for 60 days postirradi ation. Both IL-3 and IL-6 significantly enhanced the regeneration of P LTs and decreased the duration of thrombocytopenia (P = .005) without affecting PMN recovery. The radiation-induced anemia that was observed in the HSA-treated controls was less severe and resolved more quickly in the IL-6 treated animals. Sequential IL-3/IL-6 significantly incre ased the production of PLTs when compared with the HSA-treated control s (P = .003) and monkeys receiving concomitant IL-3/IL-6 (P = .041) bu t did not alter PMN levels significantly (P = .80). Coadministration o f IL-6 and IL-3 did not enhance PLT but improved PMN recovery over IL- 6 alone. In this primate model of marrow aplasia, IL-6 significantly e nhanced the regeneration of PLTs but had no significant effect on PMN production, and did not exacerbate radiation-induced anemia. Furthermo re, the use of sequentially administered IL-3 and IL-6 may improve PLT recovery as compared with concurrent IL-3/IL-6 administration, althou gh this protocol is not significantly different in effect than either cytokine alone. This is a US government work. There are no restriction s on its use.