Interleukin‐4 prevents the induction of G‐CSF mRNA in human adherent monocytes in response to endotoxin and IL‐1 stimulation

Abstract

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.