title: Enhanced production of IL-1 receptor antagonist by alveolar macrophages from patients with interstitial lung disease.
abstract: Alveolar macrophages (AM) produce various inflammatory and immunomodulatory cytokines. The objective of these experiments was to evaluate the production of IL-1ra, a specific receptor antagonist of IL-1, by AM from nonsmoking control subjects (n = 9), smoking control subjects (n = 6), and patients with interstitial lung disease (ILD) (n = 9). IL-1ra protein levels in cultured AM lysates and supernatants were determined by a specific ELISA; relative steady-state IL-1ra mRNA levels were measured using a specific cDNA probe. Before culture the isolated AM from all subject groups contained undetectable IL-1ra mRNA and no IL-1ra protein in the cell lysates as determined by ELISA. AM from nonsmoking control subjects spontaneously produced IL-1ra protein after a 20 h culture in medium, approximately 12 ng/ml with around half in cell lysates. AM from smoking control subjects produced levels of IL-1ra that were similar to the levels in AM from nonsmokers. In contrast, AM from nonsmoking ILD patients (n = 6) produced high levels of IL-1ra spontaneously (approximately 28 ng/ml), with no enhancement observed when cultured on adherent IgG. Interestingly, AM from smoking ILD patients (n = 3) produced lower levels of IL-1ra protein (approximately 11 ng/ml) that were comparable to levels noted in smoking control subjects. AM from all three types of subjects produced decreased amounts of IL-1ra in response to LPS and enhanced amounts in response to GM-CSF. In general, IL-1ra steady-state mRNA levels correlated with protein production.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Rheumatology Section, Denver VA Medical Center (111G), CO 80220.
authors.forename: R W
authors.initials: RW
authors.lastname: Janson
authors.forename: T E
authors.initials: TE
authors.lastname: King
authors.forename: K R
authors.initials: KR
authors.lastname: Hance
authors.forename: W P
authors.initials: WP
authors.lastname: Arend
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000473:pathology; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014176:Protein Biosynthesis; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D012907:Smoking / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor