Efficacy of recombinant human granulocyte-macrophage colony-stimulating factor in rhesus monkeys

Abstract

The glycosylated and the non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) expressed in Chinese hamster ovary cells and E. coli, respectively, were administered in rhesus monkeys either by the subcutaneous (three times daily) or intravenous route (6-hr infusions) for seven consecutive days. Within 24 hr peripheral white blood cells (WBC) increased 2-3 fold over normal values. Thereafter, the WBC increased steadily in a dose-dependent manner to reach maximum levels on the last day of or one day after the treatment period. The differential counts showed that neutrophils contributed to 50-80%, eosinophils to 10-20%, monocytes to 2-7%, and lymphocytes to 15-30% of the WBC rise. No effect was found on platelets and erythrocytes. After termination of treatment, WBC counts returned to normal levels within one week. Subcutaneously administered CSF was more effective in inducing leukocytosis than that injected intravenously In addition to the rise in WBC, the administered rh GM-CSF also enhanced the oxidative metabolism and bactericidal activity of the circulating mature granulocytes isolated from the blood of monkeys treated with rh GM-CSF. These results show that glycosylated or non-glycosylated rh GM-CSF is both an effective stimulator of leukocytosis and a potent activator of the functional activity of mature granulocytes in vivo.