NEUTRALIZING ANTIBODIES DURING TREATMENT OF HOMOLOGOUS NONGLYCOSYLATED IL-3 IN RHESUS-MONKEYS

During administration of homologous nonglycosylated IL-3 to rhesus mon keys, reversal of hematologic effects and disappearance of side effect s suggested a neutralizing anti-IL-3 antibody response. Among a total of 20 monkeys treated with IL-3, ELISA of serial serum samples reveale d anti-IL-3 antibodies in ten animals. Antibody production tended to b e dose dependent. Triplicate subcutaneous injections and i.v. administ ration provoked earlier appearance of antibodies than single s.c. inje ction. Prolonged continuous intravenous IL-3 administration (63 and 93 days) at a dose of 1 mu g/kg/day did not result in antibody productio n. Among a total of eight animals with sufficiently high titers to all ow for antibody purification, seven appeared to have generated antibod ies that neutralized the biologic activity of IL-3 in vitro. In six mo nkeys, the response to IL-3 decreased while antibody titers rose, stro ngly suggesting neutralization of IL-3 in vivo. It is concluded that r ecombinant, nonglycosylated IL-3 as used in this study may elicit a ne utralizing antibody response.