title: Increased TNF-alpha secretion by alveolar macrophages from patients with rheumatoid arthritis.
abstract: Tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) production by alveolar macrophages (AM) was evaluated in 17 rheumatoid arthritis (RA) patients without interstitial lung disease (ILD, Group 1) and 14 RA patients with clinical ILD (Group 2) in comparison with 10 control subjects. AM after recovery by bronchoalveolar lavage were selected by adherence, and then supernatants were collected after 3 or 24 h of culture. Results showed no modification of IL-1 synthesis in either group of RA patients. Spontaneous TNF production was significantly increased in Group 2 (2.5 +/- 0.5 ng/ml) as well as in Group 1 (2.4 +/- 0.4 ng/ml) compared with control subjects (0.43 +/- 0.1 ng/ml, p less than 0.001). In addition, AM from patients untreated or treated exclusively by nonsteroidal antiinflammatory drugs produced similar levels of TNF, whereas those receiving corticosteroids, second-line drugs (such as sulfasalazine, aurothiomalate, and methotrexate), or the combination of both therapy regimens released significantly less TNF. Interestingly, TNF was not different in both groups, but Group 2 had a markedly increased ratio of local immune complex to albumin in bronchoalveolar lavage fluid (0.47 +/- 0.12 versus 0.07 +/- 0.02 in Group 1; p less than 0.002). TNF thus appears an additional component of RA subclinical alveolitis in RA, but its prognostic value and its precise role in lung damage remain to be determined. Development of ILD requires certainly complex interactions of synergistic factors, possibly including local immune complexes detected in BAL fluids.
authors.affiliation: Centre d'Immunologie et de Biologie Parasitaire, Unité mixte INSERM, CNRS, Lille, France.
authors.forename: P
authors.initials: P
authors.lastname: Gosset
authors.forename: T
authors.initials: T
authors.lastname: Perez
authors.forename: P
authors.initials: P
authors.lastname: Lassalle
authors.forename: B
authors.initials: B
authors.lastname: Duquesnoy
authors.forename: J M
authors.initials: JM
authors.lastname: Farre
authors.forename: A B
authors.initials: AB
authors.lastname: Tonnel
authors.forename: A
authors.initials: A
authors.lastname: Capron
mesh_terms: D000936:Antigen-Antibody Complex / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000936:Antigen-Antibody Complex; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin