Type 1/type 2 cytokine paradigm and the progression of pulmonary fibrosis

The pathogenesis of end-stage, chronic lung disease is thought to be charac terized by an initial inflammatory response followed by fibroproliferation and deposition of extracellular matrix. Many of these chronic lung disorder s share a variety of common properties, including an unknown etiology, unde fined mechanisms of initiation and maintenance, and progressive fibrosis, U nfortunately, efficacious therapeutic options are not readily available for the treatment of many chronic lung diseases, which may reflect the limited scientific and mechanistic understanding of these disorders. However, rece nt studies have shown that cytokine networks are likely operative in dictat ing the progression of these diseases, as these mediators can influence fib roblast activation, proliferation, and collagen deposition during the maint enance of chronic fibrotic lung disease. Accumulating data support the conc ept that the specific cytokine phenotype may provide a fundamental mechanis m for the regulation or continuation of the fibrotic process. For example, interferon-gamma appears to suppresses fibroblast activities, such as proli feration and collagen production, while interleukin (IL)-4 and IL-13 can au gment fibroblast growth and collagen production. Interestingly, these media tors are prototypic cytokines that functionally define either a type-1 or a type-2 immune response. Thus, experimental models of cell-mediated lung in flammation, which are characterized by either a type-1 or a type-2 response , will be useful in delineating the mechanisms that either maintain or reso lve chronic lung inflammation and accompanying fibrosis.