title: Endogenous neutralizing anti-IL-1 alpha autoantibodies in inflammatory skin diseases: possible natural inhibitor for over expressed epidermal IL-1.
abstract: Interleukin 1alpha (IL-1alpha) is thought to play a central role in inflammatory reactions of the skin. Its excessive production and discharge by keratinocytes has been implicated in psoriasis, bullous diseases and other skin diseases. In addition to the type 2 IL-1 receptor and the IL-1 receptor antagonist, anti-IL-1 antibody in human serum has been proposed as a potential means to down regulate systemic responses attributable to IL-1. However, the relationship of these antibodies to disease and particularly to disease pathogenesis is still unclear. To understand this relationship, we characterized the anti-IL-1 autoantibody in sera from various skin diseases. IL-1alpha and IL-1beta radioimmunoassay, and immuno-blotting study showed the existence of IL-1alpha autoantibody but not autoantibodies to IL-1beta or pro-IL-1beta. High titer of anti-IL-1alpha autoantibodies were detected in the sera from inflammatory skin diseases with epidermal injury, including psoriasis, palmoplantar pustulosis, pustular psoriasis, pemphigus and lichen planus. In contrast, few samples from non-epidermodestructive bullous pemphigoid, atopic dermatitis and healthy normal controls had autoantibodies. The titer of anti-IL-1alpha autoantibodies showed some relation to the clinical course of psoriasis and pemphigus. Anti-IL-1 autoantibody neutralized rhIL-1alpha in D10.G4 assay and inhibited receptor binding of FITC-rhIL-1alpha. Taken together present data, the keratinocyte derived IL-1alpha could be a source of autoantigen that provokes production of endogenous anti-IL-1alpha autoantibody, which may regulate IL-1alpha mediated cutaneous inflammation.
authors.affiliation: Department of Dermatology, Mie University School of Medicine, Japan. h-mizuta@clin.medic.mie-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Mizutani
authors.forename: Y
authors.initials: Y
authors.lastname: Ohmoto
authors.forename: T S
authors.initials: TS
authors.lastname: Kupper
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000097:blood* / Q000276:immunology* / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology*; D007700:Kinetics; D008010:Lichen Planus / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D010391:Pemphigoid, Bullous / Q000097:blood / Q000276:immunology; D010392:Pemphigus / Q000097:blood / Q000276:immunology; D011565:Psoriasis / Q000097:blood / Q000276:immunology; D011863:Radioimmunoassay; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007375:Interleukin-1; D017472:Receptors, Interleukin-1