Immunological modulation of dermal fibroblasts in scleroderma.

Scleroderma can be considered as a model to study the mechanism of fibrosis. Lymphocytes and monocytes/macrophages are recruited during the inflammatory process associated with this disorder. These activated blood cells release a series of factors--lymphokines and monokines--which in turn recruit more fibroblasts, possibly stimulate their proliferation, and regulate their synthesis of collagen and glycosaminoglycans. These factors represent both positive and negative modulators for these processes. It may be the absence of an inhibitory factor(s) and/or presence of other stimulator(s) which allow the fibroblast to synthesize collagen in an uncontrolled manner, leading to the increased accumulation of this protein in the dermis. Although there is an increase in collagen accumulation in vitro, the ratio of type I/type III collagen remains unaltered. It has been suggested that an increase in T-helper cells could explain the production of collagen stimulatory lymphokines. Collagen production may also be regulated by a feedback mechanism involving the amino and carboxyl propeptides of procollagen. In scleroderma this mechanism may be altered by the lymphokine/monokine factor(s) which affect collagen synthesis. Fibrosis probably is not the primary event in scleroderma but represents the final or terminal stage of the disease. Future research on the interactions which take place between the cells of the immune system and fibroblasts may clarify the mechanism of fibrosis in scleroderma and other disorders.