Cytokine Networks in the Regulation of Inflammation and Fibrosis in the Lung (Part 1)

In: Pulmonary function

7 Nov 2012

Cytokine Networks in the Regulation of Inflammation and Fibrosis in the Lung (Part 1)Despite constant exposure to inhaled particulates and antigens, excess scar tissue and chronic inflammation do not accumulate in normal lungs. In addition, acute pneumonias, even those with frank necrosis, can heal without excess scarring. In contrast, chronic inflammation and tissue fibrosis cause significant morbidity and mortality in granulomatous and interstitial lung , and in the chronic phases of the adult respiratory distress syndrome. These different outcomes clearly demonstrate the complexity of the processes that regulate inflammation and fibrosis in the lung. Inflammation and fibrosis can be stimulated when needed to eradicate and wall off invading organisms, respond to noxious insults, and allow for normal wound healing and anabolism. In normal subjects, they are inhibited when healing is complete, resulting in the restoration of normal or near normal tissue architecture.
One of the most prominent histologic features of the granulomatous and interstitial diseases is the close approximation of mononuclear cells, fibroblasts, and fibroblast secretory products such as collagen. This finding led to the assumption that the mononuclear cells produced a small number of soluble factors that were responsible for initiating and/or perpetuating the fibrotic response. Support for this concept came from early studies that demonstrated that factors released by mononuclear cells can alter fibroblast proliferation, collagen biosynthesis,  glycosaminoglycan biosynthesis, and chemotaxis. However, we now know that this concept is overly simplistic. Mononuclear cell-fibroblast interactions are not mediated by the individual effects of a small number of molecules. Instead, like all cell-cell communications, they are the result of complex networks of interacting cytokines. Thus, one must understand cytokine-cytokine interactions, as well as the effects of individual cytokines to truly understand the processes regulating a biologic event. These studies have also demonstrated that cellcell communications in the lung, as in all other organs, are bidirectional. Mononuclear cells not only regulate fibroblast function, fibroblasts, in turn, elaborate cytokines that regulate inflammatory cell function.


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