INTRAVENOUSLY ADMINISTERED MACROPHAGE-COLONY-STIMULATING FACTOR (M-CSF) SPECIFICALLY ACTS ON THE SPLEEN, RESULTING IN THE INCREASING AND ACTIVATING SPLEEN MACROPHAGES FOR CYTOKINE PRODUCTION IN MICE

IL-6 was transiently expressed in sera of mice after a bolus intraveno us injection with LPS and it peaked 2 h later. Intravenous administrat ion of M-CSF at 250 mu g/kg/day for 5 days prior to an injection of 25 mu g/kg of LPS elevated the serum IL-6 level 10-fold higher than that of mice which were not given M-CSF. Although M-CSF had no effect on t he number of macrophages in alveoli and peritoneal cavity, it tripled the number of spleen macrophages and increased macrophage-progenitor c ells 7-fold when injected intravenously. Spleen macrophages from M-CSF -injected mice produced 5-fold more IL-6 in response to LPS-stimulatio n in-vitro. However, M-CSF-injection had lesser effects on LPS-induced IL-6 production from liver, alveolar and peritoneal macrophages. Exog enously administered M-CSF was detected at higher concentration and fo r longer duration in the spleen than in any other organs examined. Spl een macrophages incubated in-vitro with more than 1000 U/ml of M-CSF f or 3 days also produced more LPS-induced IL-6 than untreated cells. Th ese results indicate that intravenously administered M-CSF not only en hances macrophage development in the spleen, but also primes mature ma crophages for cytokine production. (C) 1997 Elsevier Science B.V.