ENHANCED IL-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA RELEASE AND MESSENGER-RNA EXPRESSION IN MACROPHAGES FROM IDIOPATHIC PULMONARY FIBROSIS OR AFTER ASBESTOS EXPOSURE

Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic inters titial lung diseases characterized by alveolar wall fibrosis with accu mulation of extracellular matrix, interstitial remodeling, and increas ed numbers Of activated alveolar macrophages. Animal models and in vit ro studies have shown that macrophage cytokines, namely IL-1beta and T NF-alpha, play significant roles in the development of fibrosis. We fo und significant increases for TNF-alpha release in both diseases (p < 0.01) and a significant increase for IL-1beta release in asbestosis co mpared to normal controls (p < 0.01). Also, the mRNA expression of the se cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha releas e in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, cro cidolite, amosite asbestos, and silica stimulated IL-1beta and TNF-alp ha release and up-regulated their respective mRNA in macrophages or mo nocytes. To evaluate the role of IL-1beta and TNF-alpha in the accumul ation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after s hort term (2 h) serum-free exposure to recombinant cytokines. Both cyt okines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in th e lower respiratory tract in IPF and asbestosis.