Anti-TGFβ1 antibody for modulation of expression of endogenous transforming growth factor beta 1 to prevent fibrosis after plastic surgery in rats

The cytokine transforming growth factor beta 1 (TGFbeta(1)) substantially influences synthesis of extracellular matrix, fibrosis, and neoangiogenesis during wound heating in a dose dependent manner. We carried out experiments in rats to measure the degree of reduction of disorders of wound heating and fibrosis produced by inhibition of endogenous, TGFbeta(1) by potyclonal antibodies (poAB). A free myocutaneous gracilis,flap was transplanted from the groin to the neck region in 30 Wistar rats (300-450g body weight). In 15 animals intraoperatively and daily from days 3 to 7 postoperatively, 1 mug anti-TGFbeta(1) poAB in 500 mul of phosphate buffered saline (PBS) were injected into the neck region. Fifteen animals served as controls. On postoperative days 3, 4, 5, 7, 14, and 28 the expression of endogenous TGFbeta1 in cytoplasm was analysed by immunohistochemistry (ABC-POX; AEC), in situ hybridisation of TGFbeta(1) -mRNA, and Sirus Red staining of collagen matrix; it was quantified using labelling indices. Neutralisation of the TGFbeta1 activity by specific poAB resulted in inhibition of the cytoplasmatic expression compared with untreated animals. In the transition area between grafted tissue and graft bed, a significant reduction of TGFbeta(1) expression (mean (S.D.) 34.7 (6.5)) was found from day 5 in the group treated with anti-TGFbeta1 poAB compared with the control group (mean (S.D.) 48.1 (6.6)) (P < 0.03). Up to day 14 the endogenous expression of TGFbeta(1) (mean (S.D.) 30.0 (2.8)) was reduced after the application of anti-TGFbeta(1) poAB compared with the control group (mean (S.D.) 44.0 (12.3)). Sirus Red staining indicated a more complex packed structure and generally more prominent collagen types I-IV fibres in untreated animals than in animals that were given anti-TGFbeta(1) poAB. Expression of TGFP-mRNA by in situ hybridisation was reduced in fibroblasts in animals that were given anti-TGFbeta(1) poAB. The results indicate that anti-TGFbeta(1) might improve the heating of free flaps in the graft beds of patients who are prone to excessive fibrosis. (C) 2004 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.