DIFFERENTIAL PROLIFERATIVE CHARACTERISTICS OF ALVEOLAR FIBROBLASTS ININTERSTITIAL LUNG-DISEASES - REGULATIVE ROLE OF IL-1 AND PGE(2)

FIBROBLASTS (Fb) from patients with sarcoidosis (SA) and hypersensitiv ity pneumonitis (HP) exhibited a lower proliferative capacity compared with Fb obtained from control (CO) and diffuse interstitial fibrosis patients (DIF). Proliferation of Fb from SA or HP patients was suppres sed by autologous LPS-stimulated alveolar macrophages (AM) supernatant s but not by those from CO patients. Similarly, alveolar macrophages ( AM) derived supernatant, obtained from CO, did not suppress the prolif eration of SA and HP Fb. AM from SA and HP patients secreted higher am ounts of IL-1 alpha and beta compared with controls and compared with Fb from SA and HP patients. Steady levels of IL-1 alpha and beta mRNA were expressed in unstimulated and stimulated cultures. Fb from SA and HP patients could be stimulated by LPS to secrete significantly highe r levels of PGE(2) than those detected in supernatants from LPS stimul ated mb of DIF patients. Only the proliferation of Fb from SA and HP p atients was sensitive to amounts of IL-1 equivalent to those detected in the lung of these diseases. As SA and HP are two diseases where irr eversible deterioration occurs in only 20% of the patients, we hypothe size that mediators in the lung may modulate Fb proliferation. IL-1 of AM origin. and PGE(2) of Fb origin secreted at high levels, may be ca ndidates for this suppression because it was abrogated by anti IL-1 be ta and indomethacin.