Enhanced production of IL-1 receptor antagonist by alveolar macrophages from patients with interstitial lung disease.

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)