title: Crystal-induced neutrophil activation. V. Differential production of biologically active IL-1 and IL-1 receptor antagonist.
abstract: Neutrophils produce IL-1 when stimulated by monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals. Neutrophils also generate the IL-1R antagonist (IL-1Ra), especially when incubated with granulocyte-macrophage CSF (GM-CSF) or TNF-alpha. We studied the simultaneous expression of IL-1 and IL-1Ra by GM-CSF- or TNF-alpha-treated neutrophils activated by MSU or CPPD. Neutrophils incubated with GM-CSF or TNF-alpha produced approximately 300 or 200 times more IL-1Ra than IL-1, respectively. Suboptimal concentrations of MSU or CPPD induced low amounts of IL-1 without affecting IL-1Ra. Interaction of GM-CSF- and TNF-alpha-treated neutrophils with MSU or CPPD up-regulated IL-1 while simultaneously down-regulating IL-1Ra. As a result, the bioactivity of IL-1 secreted was enhanced. Synergistic increases of IL-1 (but not IL-1Ra) mRNA levels were noted in GM-CSF- or TNF-alpha-treated neutrophils exposed to CPPD. Treatment of neutrophils with colchicine before incubation with GM-CSF or TNF alpha, inhibited crystal-induced IL-1 by 50 to 55%, but failed to significantly affect IL-1Ra. The IL-1Ra to IL-1 ratio was significantly increased by 185 to 220%. These results demonstrate that IL-1 and IL-1Ra production by human neutrophils are differentially regulated, that the combined presence of GM-CSF or TNF-alpha and microcrystals favor the production of biologically active IL-1 over that of IL-1Ra, and that colchicine selectively inhibits IL-1 without affecting IL-1Ra production.
authors.affiliation: Laval University Hospital Center, Québec, Canada.
authors.forename: C J
authors.initials: CJ
authors.lastname: Roberge
authors.forename: R
authors.initials: R
authors.lastname: de Médicis
authors.forename: J M
authors.initials: JM
authors.lastname: Dayer
authors.forename: M
authors.initials: M
authors.lastname: Rola-Pleszczynski
authors.forename: P H
authors.initials: PH
authors.lastname: Naccache
authors.forename: P E
authors.initials: PE
authors.lastname: Poubelle
mesh_terms: D002131:Calcium Pyrophosphate / Q000494:pharmacology*; D003078:Colchicine / Q000494:pharmacology; D003460:Crystallization; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D014527:Uric Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003078:Colchicine; D002131:Calcium Pyrophosphate