P-23   SUCCESSFUL TREATMENT OF ALOPECIA AREATA WITH ANTI-INTERFERON (IFN) gamma

N. Sharova1, N. Korotky1, B. Skurkovich2 3, S. Skurkovich2. Department of Skin and Venereal Diseases1, Russian State Medical University, Moscow, Russia; Advanced Biotherapy Labs, Rockville2, MD USA; Brown Medical School3, Providence, RI USA.

In 1974 we proposed that the main cause of autoimmune disease (AD) is abundant IFN production and that anti-IFN can be therapeutic (S. Skurkovich, Nature, 1974;247:551-2). We later also proposed to remove tumor necrosis factor (TNF)-alpha, induced by IFN-gamma, to treat various autoimmune conditions (J IFN Sci 1989;9S). Alopecia areata is an AD mediated by the autoactivation of Th-1 cells, which produce significant amounts of interferon-gamma. The hyperproduction of IFN-gamma is one of the most significant factors in the damage to follicular cells. Under the influence of high levels of IFN-gamma, an increase in the cytolytic activity of NK cells, activation of T-lymphocytes (CD4+), and the expression of the Fas-ligand on macrophages, lymphocytes and target cells with which they interact, was observed. The neutralization of excess IFN-gamma can lead to the reduction of autoimmune inflammation. 17 patients with alopecia areata, 10 to 32 years of age, duration of illness from 4.5 months to 5.5 years, were treated with anti-IFN-gamma antibodies. Most patients had patches of hair loss from 3.5 to 14 cm in diameter, with brows and eyelashes partly or completely absent. Anti-IFN-gamma (F(ab)2 fragments generated from goat antihuman IFN-gamma were administered intradermally or intramuscularly for 5 days at 2.0 ml/day (33 mg/ml protein, neutralizing activity >66 micrograms/ml). At 4 weeks from start of treatment, 8 patients had vellus hair growth in the areas of hair loss. Four patients had growth of brows and eyelashes. At 8 weeks, in 14 patients terminal hair appeared in the lesions. After 16 weeks, the hair of 10 patients was restored with 4 achieving significant improvement in the form of active growth of vellus hair in the lesions. At this time in 2 patients there was some vellus hair in the bald areas of the scalp and partial regrowth of brows and eyelashes. No effect from the therapy was observed in 1 patient. We believe that anti-IFN-gamma antibodies are very promising in the treatment of alopecia areata. Anti-TNF-alpha may also be effective in this disease. In the future, we plan to give humanized monoclonal antibodies to IFN-gamma to these patients.