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 abnormalities 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 elevated levels of circulating IgE levels in AD patients. We sought to determine 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 patients demonstrated reductions in WBC, eosinophil, and lymphocyte counts. Compared to normals, there was a reduced CD4/CD8 ratio in AD patients among activated, 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 lymphocytes (r = 0.9, P = 0.04). The data indicate two potential modes of action for INF-gamma in AD. One mechanism represents normalization of selected immunologic abnormalities in AD; a second mechanism may be the modest reduction of circulating inflammatory cells. Adequacy of IFN-gamma therapy of AD may depend on bringing about these changes.
Department of Dermatology, University of Michigan Medical School and Veterans Affairs Medical Center, Ann Arbor, Michigan 48109, USA.
C N
CN
Ellis
S R
SR
Stevens
B K
BK
Blok
R S
RS
Taylor
K D
KD
Cooper
D000328:Adult; D018951:Antigens, CD20 / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D016516:CD4-CD8 Ratio; D003876:Dermatitis, Atopic / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D004804:Eosinophils / Q000166:cytology; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D018655:Lymphocyte Count / Q000187:drug effects; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D010919:Placebos
D018951:Antigens, CD20; D010919:Placebos; D007371:Interferon-gamma