Production of soluble tumor necrosis factor receptors and tumor necrosis factor-alpha by alveolar macrophages in sarcoidosis and extrinsic allergic alveolitis.
BACKGROUND
Alveolar macrophage (AM)-derived tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of sarcoidosis and extrinsic allergic alveolitis (EAA). The effects of TNF-alpha are mediated by membrane TNF receptor (mTNFR)-1 and mTNFR-2, and can be blocked by soluble TNF receptor (sTNFR)-1 and sTNFR-2.


METHODS
We measured the production of the two sTNFRs and TNF-alpha in AM culture supernatants from 10 patients with active sarcoidosis, 12 patients with EAA, and 9 control subjects using an enzyme-linked immunosorbent assay method.


RESULTS
Compared with control subjects, the spontaneous and lipopolysaccharide (LPS)-stimulated production of sTNFR-1, sTNFR-2, and TNF-alpha was significantly increased in patients with sarcoidosis and EAA. The concentrations of both sTNFRs, but especially of sTNFR-2, were closely related to those of TNF-alpha. The LPS-induced increase was 1.5-fold for sTNFR-1, at least fourfold for sTNFR-2, and at least 25-fold for TNF-alpha in all study populations.


CONCLUSIONS
These results indicate that AMs can release the two sTNFRs in relation to TNF-alpha. sTNFR-2 may be more liable to shedding than sTNFR-1. Both sTNFR-1 and sTNFR-2 may be involved in the pathogenesis of sarcoidosis and EAA, possibly as counterregulators of TNF-alpha.
Dai
Huaping
H
Department of Penumology and Allergy, Ruhrlandklinik, Medical Faculty, University of Essen, Essen, Germany.
Guzman
Josune
J
Chen
Baomin
B
Costabel
Ulrich
U
D000328:Adult; D000542:Alveolitis, Extrinsic Allergic / Q000097:blood* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood* / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood / Q000502:physiology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood / Q000502:physiology; D012507:Sarcoidosis / Q000097:blood* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha