Transforming Growth Factor-β in Thermally Injured Patients with Hypertrophic Scars: Effects of Interferon α-2b

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Abstract

Hypertrophic scarring is a common dermal fibroproliferative disorder that leads to poor quality wound healing, prolongs rehabilitation, and increases morbidity following major thermal and other injuries to the deep dermis. Local and systemic transforming growth factor (TGF)-β has been implicated as a fibrogenic cytokine in the pathogenesis of many fibrotic disorders, whereas interferon (IFN) α-2b may improve the pathologic features of dermal fibrosis directly or by antagonizing the effects of TGF-β and histamine.

Nine patients with severe hypertrophic scarring were evaluated for 8 weeks before treatment with subcutaneous recombinant IFN α-2b, 2 × 106 IU three times per week for 24 weeks. Clinical assessment was performed using standardized photography, a burn scar assessment tool, and serial scar volume measurements. Monthly measurements of serum TGF-β and plasma Nt-methylhistamine were made prior to, during, and after IFN α-2b therapy and compared with 27 age-matched controls. Serial biopsies of the hypertrophic scars and normal skin were performed for evaluation of mast cell numbers.

Significant improvement in scar assessment occurred in 7 of 9 patients, and 3 of 9 demonstrated significant reductions in scar volume with interferon therapy beyond that occurring during the 8-week control period. For the entire group, mean rates of improvement were significantly better during interferon therapy with no recurrence following treatment. Before interferon therapy, serum TGF-β was significantly higher in the burn patients with hypertrophic scarring than in a control population (123.04 ± 36.48 vs. 56.85 ± 8.38 ng/ml, p < 0.05). Within 3 months of IFN α-2b therapy, serum TGF-β levels fell significantly and remained within the normal range during therapy and after interferon therapy was stopped. Plasma NT-methylhistamine levels were also significantly elevated in the hypertrophic scar patients as compared with age and sex-matched controls (153.6 ± 92.07 vs. 48.3 ± 28.9 pg/ml, p < 0.05), and significant reductions were achieved with interferon therapy and maintained after interferon was discontinued. Paired biopsies of hypertrophic scarring and normal tissue demonstrated increased numbers of mast cells in hypertrophic scars compared with normal uninjured skin from the same patients (2.65 ± 1.63 vs. 1.04 ± 0.62 cells/high power field, p < 0.001); however, no significant change in mast cell content of the hypertrophic scars accompanied interferon therapy.

Patients with severe hypertrophic scarring demonstrate increased levels of serum TGF-β and plasma NT-methylhistamine following thermal injury. A significant clinical improvement in scar quality and volume occurred during IFN α-2b therapy, which was associated with normalization of serum TGF-β and plasma Nt-methylhistamine levels. A double-blind, placebo-controlled trial will be required to further assess the usefulness of subcutaneous treatment with IFN α-2b for the treatment of hypertrophic scarring. (Plast. Reconstr. Surg. 102: 1317, 1998.)

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