Production of interleukin-1 (IL-1) and a specific IL-1 inhibitor during human monocyte-macrophage differentiation: influence of GM-CSF.
Mononuclear phagocytes release several factors involved in host defense and inflammation. Of these, interleukin-1 (IL-1) has multiple biological activities which are controlled at different levels including modulation of gene expression, protein synthesis or secretion, and interaction with inhibitors. We have investigated the production of IL-1 alpha and beta as well as the production of a specific IL-1 inhibitor (IL-1 INH) during the in vitro maturation of human monocyte-macrophages. Highly purified monocytes isolated by counterflow centrifugal elutriation were cultured up to six weeks, producing high levels of IL-1 alpha and beta during the first week of culture. Shortly after the first week bioactivity of IL-1 decreased, preceding a decrease of IL-1 immunoreactivity. In contrast, IL-1 inhibitory activity reached a peak during the third week and remained detectable up to six weeks. Granulocyte-monocyte-colony-stimulating factor GM-CSF increased the production of IL-1 INH by approximately 20%, but did not affect IL-1 production. The IL-1 INH, apparent molecular weight approximately 23 kD, blocks the binding of [125I]IL-1 alpha to its receptor. The balance between the production of IL-1 and its antagonist may be important for the regulation of the immune response and chronic inflammation during pathological processes.
Roux-Lombard
P
P
Division of Immunology and Allergy (Hans Wilsdorf Laboratory), Hôpital cantonal universitaire, Geneva, Switzerland.
Modoux
C
C
Dayer
J M
JM
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008222:Lymphokines / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D007375:Interleukin-1; D008222:Lymphokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor