INTERLEUKIN-4 PREVENTS THE INDUCTION OF G-CSF MESSENGER-RNA IN HUMAN ADHERENT MONOCYTES IN RESPONSE TO ENDOTOXIN AND IL-1 STIMULATION

Human recombinant interleukin-4 (IL-4) was studied for its effects on the expression of granulocyte-colony stimulating factor (G-CSF) mRNA in human adherent monocytes in the absence and presence of endotoxin and interleukin 1 (IL-1). IL-4 (15 ng/ml) did not induce G-CSF transcripts in monocytes but suppressed the endotoxin-induced G-CSF expression when added simultaneously. Sequential treatment of monocytes with IL-4 followed by endotoxin suppressed G-CSF mRNA induction totally. This effect was independent of the presence of fetal bovine serum but dependent of the IL-4 dose. Comparable results were obtained with IL-1. IL-1 (50 U/ml) induced G-CSF expression in human adherent monocytes which could be counteracted by IL-4 pretreatment. In addition, it was shown that the induction of G-CSF mRNA by the calcium-ionophore A23187 or by c-AMP elevating agents could be blocked by IL-4. These suppressive effects of IL-4 were not related to changes in the half-life of G-CSF mRNA and were independent of protein synthesis. Finally it was demonstrated that IL-4 had comparable effects on the G-CSF secretion of endotoxin and IL-1 stimulated human monocytes by using a murine bone marrow assay. These results indicate that IL-4 down-regulates the expression of G-CSF gene and secretion of proteins in human activated monocytes.