Th1 versus Th2 Inflammation in Mesenchymal Cell Survival and Lung Fibrosis Even though polypeptide growth elements which include PDGF and EGF ligands are crucial for keeping mesenchymal cell survival and proliferation, the survival of those cells can also be determined in huge portion by the kind of inflamma tory microenvironment. Within these microenviron ments, mesenchymal cells are bathed inside a selection of cytokines, chemokines and lipid mediators that influence cell survival. Some of these aspects that modulate mesenchymal cell survival and phenotype are illustrated in Figure 3. Inflammatory reactions are characterized by the infiltration of mononuclear cells including macro phages, lymphocytes, neutrophils and eosinophils. Despite the fact that inflammation ordinarily precedes fibrosis, evi dence from experimental animal models of fibrosis and clinical studies exactly where anti inflammatory drugs have little impact on lung fibrosis suggest that inflammation may not be essential for fibrogenesis.
Even so, the idea that inflammation and fibrosis could be distinct processes is probably an oversimplification, because it is apparent that inflammatory cytokines and chemokines have potent modulatory effects on growth element activity. For exam ple, through asthma, infiltrating Th2 lymphocytes pro duce interleukin 13, a key cytokine that mediates various phenotypes find out this here of airway remodeling, including mucus cell metaplasia, eosinophilia, airway smooth muscle thickening and airway fibrogenesis. IL 13 has also been proposed to play a function in some ani mal models of interstitial lung fibrosis models, which includes bleomycin and FITC. Transgenic mice that overex press IL 13 create tissue fibrosis by way of production and activation of TGF b1.
Studies employing a bleomy cin induced pulmonary fibrosis demonstrated that IL 13 signaling via the IL 13a2 receptor is involved in induction of TGF b1 production and fibrosis. The proliferation of lung myofibroblasts in response to IL 13 is mediated by way of the autocrine selleck release of PDGF AA and PDGF CC. As illustrated in Figure 3, IL 13 generated for the duration of a Th2 inflammatory response is significant in airway and interstitial fibrosis due in component to its ability to improve PDGF and TGF b1, which in turn influence mesenchymal cell survival and collagen deposition. While IL 13 seems to become central for the patho genesis of airway fibrosis in asthma and in some ani mal models of interstitial fibrosis, other models of lung fibrosis are certainly not dependent on Th2 inflammation and IL 13. As an example, V2O5 induced lung fibrosis in mice functions Th1 inflammation and elevated levels of interferon g and IFN inducible cytokines in addition to elevated levels of profibrogenic growth variables and collagen with no apparent increases in IL 13.