title: Modulation of the acute phase response by altered expression of the IL-1 type 1 receptor or IL-1ra.
abstract: A complete understanding of the role for endogenously produced interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) in the acute phase response to inflammation remains unknown. In the present studies, knockout mice lacking either a functional IL-1 type I receptor (IL-1RI(-/-)), a TNF type I receptor (TNFR-I(-/-)), or both IL-1 type I and TNF type I receptors (IL-1RI(-/-)/TNFR-I(-/-)) received a turpentine abscess. Additional mice deficient in IL-1ra protein (IL-1ra(-/-)) or overexpressing IL-1ra protein (IL-1ra(tg)) were similarly treated. After a turpentine abscess, IL-1 receptor knockout mice exhibited an attenuated inflammatory response compared with wild-type or animals lacking a functional TNFR-I. Mice overexpressing IL-1ra also had an attenuated hepatic acute phase protein response, whereas IL-1ra knockout mice had a significantly greater hepatic acute phase response. We conclude that the inflammatory response to a turpentine abscess is the result of a balance between IL-1ra expression and IL-1 binding to its type I receptor. Endogenously produced IL-1ra plays a central role in mitigating the magnitude of the IL-1-mediated inflammatory response and, ultimately, the outcome to a turpentine abscess.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Josephs
authors.forename: C C
authors.initials: CC
authors.lastname: Solorzano
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.forename: J J
authors.initials: JJ
authors.lastname: Rosenberg
authors.forename: D
authors.initials: D
authors.lastname: Topping
authors.forename: A
authors.initials: A
authors.lastname: Abouhamze
authors.forename: S L
authors.initials: SL
authors.lastname: Mackay
authors.forename: E
authors.initials: E
authors.lastname: Hirsch
authors.forename: D
authors.initials: D
authors.lastname: Hirsh
authors.forename: M
authors.initials: M
authors.lastname: Labow
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000038:Abscess / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D000210:Acute-Phase Reaction / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D000855:Anorexia / Q000276:immunology / Q000503:physiopathology; D001066:Appetite / Q000276:immunology; D001835:Body Weight; D002100:Cachexia / Q000276:immunology / Q000503:physiopathology; D004435:Eating; D005260:Female; D015870:Gene Expression / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000276:immunology; D007509:Irritants; D008099:Liver / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D012795:Sialoglycoproteins / Q000235:genetics*; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014425:Turpentine
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D007509:Irritants; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D014425:Turpentine