TH1 AND TH2 RESPONSES REGULATE EXPERIMENTAL LUNG GRANULOMA DEVELOPMENT

The pathogenesis of chronic interstitial lung disease is often charact erized as an intense inflammatory response with accompanying fibroprol iferation and deposition of extracellular matrix. Certain of these lun g disorders share common characteristics, including an unknown etiolog y, ill defined mechanisms of initiation and maintenance, and end-stage fibrosis. Progressive pulmonary inflammation, as can occur in disease s such as idiopathic pulmonary fibrosis and end-stage sarcoidosis, is associated with substantial morbidity and mortality. Unfortunately, ef ficacious therapeutic options are not available for the treatment of t hese diseases, reflecting the limited scientific understanding of thes e disorders. However, it is likely that cytokine networks are operativ e in dictating the progression of these diseases. Recent studies show that various cytokines affect fibroblast activation, proliferation, an d collagen deposition during the evolution of chronic fibrotic lung di sease. In particular, gamma interferon suppresses such fibroblast acti vities as proliferation and collagen production, while interleukin-4 a ugments fibroblast growth and collagen production. Interestingly, thes e two mediators are the prototypic cytokines which functionally define either a Th1 or a Th2 response. Thus, experimental models of granulom atous lung inflammation, which are characterized by either a Th1 or a Th2 response, will be useful in delineating the mechanisms which maint ain and resolve chronic granulomatous lung inflammation. These experim ental systems will prove to be especially important as the degree of i nflammation and fibroblast activation/proliferation during the pathoge nesis of chronic pulmonary inflammation may be dependent upon a balanc e of Th1- and Th2-like cytokines which are expressed during the evolut ion of the disease.