title: IL-1 beta production by human polymorphonuclear leucocytes stimulated by anti-neutrophil cytoplasmic autoantibodies: relevance to systemic vasculitis.
abstract: Neutrophils accumulate in the acute blood vessel lesions of patients with autoimmune systemic vasculitis. They have been shown previously to produce the cytokine IL-1 beta in response to stimulation with TNF. This study demonstrates that neutrophils can be stimulated by anti-neutrophil cytoplasmic antibodies (ANCA), which are present in patients with systemic vasculitis, to express mRNA and protein for IL-1 beta. Both human ANCA and MoAbs to a variety of autoantigens recognized by ANCA, including proteinase 3, myeloperoxidase, bactericidal/permeability increasing protein and elastase, are effective. This response can be inhibited by actinomycin and cycloheximide, suggesting a requirement for de novo protein synthesis. IL-1 beta production can be inhibited by pooled human intravenous immunoglobulins but not by FK506 or cyclosporin A. These data suggest that ANCA in patients with active vasculitis may stimulate neutrophils to produce cytokines. It is hypothesized that cytokine production from neutrophils that accumulate in significant numbers in vasculitic lesions contribute to and augment the local inflammatory response by the activation of vascular endothelial cells and infiltrating leucocytes.
authors.affiliation: Department of Medicine, CCRIS, Medical School, Birmingham University, Edgbaston, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Brooks
authors.forename: W J
authors.initials: WJ
authors.lastname: King
authors.forename: D J
authors.initials: DJ
authors.lastname: Radford
authors.forename: D
authors.initials: D
authors.lastname: Adu
authors.forename: M
authors.initials: M
authors.lastname: McGrath
authors.forename: C O
authors.initials: CO
authors.lastname: Savage
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001167:Arteritis / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology; D001798:Blood Proteins / Q000276:immunology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D014890:Granulomatosis with Polyangiitis / Q000378:metabolism*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D019272:Leukocyte Elastase / Q000276:immunology; D008565:Membrane Proteins; D053146:Myeloblastin; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009195:Peroxidase / Q000276:immunology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D023181:Antimicrobial Cationic Peptides; D001324:Autoantigens; D001798:Blood Proteins; D016756:Immunoglobulins, Intravenous; D007375:Interleukin-1; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; C021623:bactericidal permeability increasing protein; D003609:Dactinomycin; D003513:Cycloheximide; D009195:Peroxidase; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase; D053146:Myeloblastin