Th1 and Th2 responses regulate experimental lung granuloma development.
The pathogenesis of chronic interstitial lung disease is often characterized as an intense inflammatory response with accompanying fibroproliferation and deposition of extracellular matrix. Certain of these lung disorders share common characteristics, including an unknown etiology, ill defined mechanisms of initiation and maintenance, and end-stage fibrosis. Progressive pulmonary inflammation, as can occur in diseases such as idiopathic pulmonary fibrosis and end-stage sarcoidosis, is associated with substantial morbidity and mortality. Unfortunately, efficacious therapeutic options are not available for the treatment of these diseases, reflecting the limited scientific understanding of these disorders. However, it is likely that cytokine networks are operative in dictating the progression of these diseases. Recent studies show that various cytokines affect fibroblast activation, proliferation, and collagen deposition during the evolution of chronic fibrotic lung disease. In particular, gamma interferon suppresses such fibroblast activities as proliferation and collagen production, while interleukin-4 augments fibroblast growth and collagen production. Interestingly, these two mediators are the prototypic cytokines which functionally define either a Th1 or a Th2 response. Thus, experimental models of granulomatous lung inflammation, which are characterized by either a Th1 or a Th2 response, will be useful in delineating the mechanisms which maintain and resolve chronic granulomatous lung inflammation. These experimental systems will prove to be especially important as the degree of inflammation and fibroblast activation/proliferation during the pathogenesis of chronic pulmonary inflammation may be dependent upon a balance of Th1- and Th2-like cytokines which are expressed during the evolution of the disease.
Kunkel
S L
SL
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Lukacs
N W
NW
Strieter
R M
RM
Chensue
S W
SW
D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines