The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study.
BACKGROUND
While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD.


OBJECTIVE
To characterize further the immunophenotype of infiltrating cells and the production of certain cytokines before and after treatment with topical tacrolimus and hydrocortisone butyrate.


METHODS
Nine adult patients with moderate to severe AD were treated with tacrolimus ointment, while seven control patients were treated with hydrocortisone butyrate ointment. We performed lesional skin biopsies before and after treatment. These were stained immunohistochemically with a panel of monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase, EG1, EG2, tryptase, interferon-gamma, interleukin (IL)-4, IL-5, IL-12, IL-13, receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines.


RESULTS
CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil granulocytes were significantly reduced in post-treatment tacrolimus specimens, while CD1a+ cells and mast cells were not. The expression of cytokines and chemokine receptors tested, except for CXCR3, was diminished by tacrolimus treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes, eosinophils and most cytokines than that induced by hydrocortisone butyrate.


CONCLUSIONS
Tacrolimus not only inhibits T-lymphocyte proliferation and cytokine production, but also plays an important role in the IL-12-induced shift from a T-helper (Th) 2 to a Th1 cytokine profile that characterizes the development of chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than hydrocortisone.
Caproni
M
M
Department of Dermatological Sciences, University of Florence, Via della Pergola 58/60, 50121 Florence, Italy.
Torchia
D
D
Antiga
E
E
Terranova
M
M
Volpi
W
W
del Bianco
E
E
D'Agata
A
A
Fabbri
P
P
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009824:Ointments; D018121:Receptors, Cytokine / Q000378:metabolism; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007166:Immunosuppressive Agents; D009824:Ointments; D018121:Receptors, Cytokine; D006854:Hydrocortisone; D016559:Tacrolimus