Effects of tacrolimus ointment on Toll-like receptors in atopic dermatitis.
BACKGROUND
Alterations of Toll-like receptors (TLRs) seem to play a role in susceptibility to atopic dermatitis (AD).


OBJECTIVE
To investigate the expression of TLRs in moderate to severe chronic AD in adults before and after a 3-week treatment with 0.1% tacrolimus ointment, compared with 0.1% topical hydrocortisone-17-butyrate.


METHODS
In total, 21 adult patients with AD were enrolled: 11 were given tacrolimus ointment and 10 were given hydrocortisone butyrate; a further 6 healthy adults formed the control group. The clinical efficacy of the treatment was assessed using the SCORing Atopic Dermatis (SCORAD) index. Biopsies were taken from lesional skin before and after treatment, which were stained immunohistochemically with monoclonal antibodies to TLR-1, -2, -4 and -9.


RESULTS
Both 3-week topical treatments improved signs and symptoms in all 21 patients considered, with no significant difference between the two groups. In the skin of patients with AD, TLR-1 was overexpressed and TLR-2 underexpressed compared with healthy controls, whereas no differences were found for TLR-4 and TLR-9. Staining for TLR-1 was decreased in both groups after treatment. AD specimens had higher levels of TLR-2 expression after either treatment compared with baseline, and levels were higher after tacrolimus treatment than after hydrocortisone butyrate. Neither tacrolimus nor hydrocortisone butyrate affected expression of TLR-4 or TLR-9.


CONCLUSIONS
Short-term therapy with tacrolimus ointment reduced expression of TLR-1, which may inhibit the antimicrobial potential of TLR-2, and also reversed the impairment of TLR-2 in AD lesions. Expression of TLR-4 and TLR-9 was not affected by tacrolimus.
Department of Dermatological Sciences, University of Florence, Florence, Italy. emiliano.antiga@unifi.it
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D000328:Adult; D000368:Aged; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology*; D003879:Dermatologic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009824:Ointments; D012867:Skin / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use; D051194:Toll-Like Receptor 1 / Q000187:drug effects / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000378:metabolism; D051193:Toll-Like Receptors / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
D003879:Dermatologic Agents; D007166:Immunosuppressive Agents; D009824:Ointments; C495342:TLR2 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; C007975:hydrocortisone-17-butyrate; D006854:Hydrocortisone; D016559:Tacrolimus