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.

The effects of IL‐1 and IL‐4 on the Epo‐independent erythroid progenitor in polycythaemia vera

“…Furthermore, we wondered whether IL-4 could modulate the Epo-independent colony growth because IG4 can affect the erythroid colony formation and modulate the effects of IL-1 (de Wolf et al 1991;Hart et al 1989). Furthermore, we wondered whether IL-4 could modulate the Epo-independent colony growth because IG4 can affect the erythroid colony formation and modulate the effects of IL-1 (de Wolf et al 1991;Hart et al 1989).…”

Neonatal Leukemoid Reaction and Early Development of Bronchopulmonary Dysplasia in a Very Low-Birth-Weight Infant

“…Accelerated neutrophil production can occur in neutropenic neonates after the stimulation of hematopoietic progenitors with G-CSF or GM-CSF; certainly the administration of recombinant G-CSF or GM-CSF to neonates in sufficiently high doses produced leukemoid reactions [19,20]. Monocytes and macrophages appear to be the primary source of G-CSF production in vivo [21]; IL-1·, IL-1ß, bacterial lipopolysaccharide, and other inflammatory mediators are capable of initiating G-CSF production by monocytes and macrophages [6][7][8].…”

“…An excess of inflammatory cytokines is known to cause fetal stimulation of hematopoietic progenitors with neutrophilic leukocytosis [4][5][6][7][8] and has been implicated in the sequence of inflammatory diseases during the perinatal period, namely severe respiratory distress syndrome, chronic lung disease of prematurity, periventricular white matter damage, shock and multiorgan disease [9][10][11].…”

Potential Interaction of lnterleukin-4 with Endogenous Cytokines in vivo

“…We have evaluated our data at the level of a direct effect of IL-4, and extended our analy sis to include the activities of IL-3, IL-5 and GM-CSF which, based on our data, are either induced by IL-4 or are naturally present and interact with IL-4. However, at least in vitro, IL-4 has the ability to modulate the produc tion and interact in both a positive and negative manner with many cytokines which have an effect on hemato poietic cells, such as IL-1 [44][45][46][47], IL-6 [45,[48][49][50][51][52][53], TNF-a [47,54,55], M-CSF [56,57], G-CSF [58], IL-8 [59] and IL-11 [60].…”