Interferon-gamma therapy reduces blood leukocyte levels in patients with atopic dermatitis: Correlation with clinical improvement

Atopic dermatitis (AD) is a chronic inflammatory skin disease with abnonmal ities of both cellular and humoral immunity. Subcutaneous recombinant human interferon-gamma (IFN-gamma) provides therapeutic benefit to AD patients. In contrast to expectations, IFN-gamma does not cause a decrease in the ele vated levels of circulating IgE levels in AD patients, We sought to determi ne cellular targets of IFN-gamma treatment that might explain its clinical benefit. Therefore, we evaluated blood leukocyte subsets by multiparameter flow cytometry in AD patients receiving IFN-gamma (n = 10) or placebo (n = 11) therapy compared to untreated normal volunteers (n = 14). Treated patie nts demonstrated reductions in WBC, eosinophil, and lymphocyte counts. Comp ared to normals, there was a reduced CD4/CD8 ratio in AD patients among act ivated, large mononuclear cells that was partially corrected with IFN-gamma treatment. Clinical improvement correlated with reductions in WBC (r = 0.9 , P = 0.0003), eosinophil (r = 0.7, P = 0.035) and lymphocyte (r = 0.8, P = 0.013) counts, and with normalization of the CD4/CD8 ratio among large lym phocytes (r = 0.9, P = 0.04). The data indicate two potential modes of acti o:n for INF-gamma in AD. One mechanism represents normalization of selected immunologic abnormalities in AD; a second mechanism may be the modest redu ction of circulating inflammatory cells. Adequacy of IFN-gamma therapy of A D may depend on bringing about these changes. (C) 1999 Academic Press.