Cytokine expression is downregulated by collagen-polyvinylpyrrolidone in hypertrophic scars

Abstract

We evaluated the in situ expression of adhesion molecules (E-selectin and vascular cell-adhesion molecule) and proinflammatory/fibrogenic cytokines (IL-1beta, TNF-alpha, TGF-beta1, and PDGF) in sections of normal skin, hypertrophic scar, and hypertrophic scar previously treated with an irradiated mixture of collagen-polyvinylpyrrolidone and completely resolved. Expression of these proteins was detected by indirect immunoperoxidase staining. The hypertrophic scar group displayed an increased amount of IL-1beta, TNF-alpha, TGF-beta1, and PDGF compared with the normal skin and treated scar groups. Values were statistically significant when cytokines in hypertrophic scar and hypertrophic treated sections were compared. Surprisingly, no differences were detected between normal skin and treated scars. On the other hand, differences in levels of E-selectin and vascular cell-adhesion molecule were not statistically significant between the groups, except for vascular cell-adhesion molecule, which decreased in treated scars. Also, supernatants from fibroblast cultures derived from treated hypertrophic scar, showed a reduction in TGF-beta1 and PDGF expression, although apparently collagen synthesis was not affected. Based on previous data from clinical studies in human dermal fibrosis remodeling, and the results presented here, we suggest that collagen-polyvinylpyrrolidone modulates extracellular matrix turnover, mainly of collagen, because expression levels of IL-1beta, TNF-alpha, TGF-beta1, and PDGF were diminished. We infer that collagen-polyvinylpyrrolidone participation could also modify the inflammatory process observed in hypertrophic scarring, by diminishing the expression of adhesion molecules, as a consequence of lower levels of proinflammatory cytokines, mainly IL-1beta and TNF-alpha.