| Title | Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids). | | Author(s) | Sakuma S, Higashi Y, Sato N, Sasakawa T, Sengoku T, Ohkubo Y, Amaya T, Goto T | | Institution | Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd. 1-6, Kashima 2-chome, Yodogawa, Osaka 532-8514, Japan. shozo_sakuma@po.fujisawa.co.jp | | Source | Int Immunopharmacol 2001 Jun; 1(6):1219-26. | | MeSH | Antigens, CD28
Antigens, CD3
Antigens, CD4
Betamethasone
Cell Separation
Cells, Cultured
Cytokines
Depression, Chemical
Dermatitis, Atopic
Enzyme-Linked Immunosorbent Assay
Humans
Immunosuppressive Agents
Indicators and Reagents
Methylprednisolone
Monocytes
Steroids
Tacrolimus
| | Abstract | Tacrolimus (FK506) ointment showed remarkable efficacy against atopic dermatitis in animal models and clinical trials. The suppressive effect of tacrolimus on the production of the cytokines involved in atopic dermatitis (IL-2, IL-3, IL-4, IL-5, IFN-gamma and GM-CSF) from human peripheral blood mononuclear cells (PBMC) was investigated. We constructed a new cytokine production system in which T cells are activated by direct stimulation in vitro with anti-CD3/CD2 or anti-CD3/CD28 antibody combination. Tacrolimus inhibited the production of these cytokines by both stimulations. In a comparative study with steroids (alclometasone dipropionate and betamethason valerate) in anti-CD3/CD2 system, tacrolimus and both steroids inhibited Th1 cytokines (IL-2, IFN-gamma), Th2 cytokines (IL-4, IL-5) and IL-3, GM-CSF (produced by both Th1 and Th2). The suppressive effect of tacrolimus on cytokine production was stronger than that of alclometasone dipropionate and equal to or stronger than that of betamethason valerate. The effective dose of tacrolimus (IC50, 0.02-0.11 ng/ml) is almost the same as for Th1 and Th2 cytokines, and 1 ng/ml of tacrolimus suppressed all cytokines completely. These results suggest that tacrolimus suppresses the allergic cytokines from T cells, and that tacrolimus ointment is effective against atopic dermatitis through the inhibition of cytokine production. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11407316 |
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