Tacrolimus inhibits cytokine production and chemical mediator release following antigen stimulation of passively sensitized human lung tissues

Citation
N. Matsuo et al., Tacrolimus inhibits cytokine production and chemical mediator release following antigen stimulation of passively sensitized human lung tissues, ANN ALLER A, 86(6), 2001, pp. 671-678
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Clinical Immunolgy & Infectious Disease
Journal title
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
ISSN journal
1081-1206 → ACNP
Volume
86
Issue
6
Year of publication
2001
Pages
671 - 678
Database
ISI
SICI code
1081-1206(200106)86:6<671:TICPAC>2.0.ZU;2-Z
Abstract
Background: The immunosuppressive effects of tacrolimus are mediated by inh ibition of cytokine production by inflammatory cells. The role of tacrolimu s on cytokine production and release of chemical mediators in asthma is not known at present. Objectives: We compared the effects of tacrolimus on interleukin (IL)-5 and tumor necrosis factor-alpha (TNF-alpha) production and chemical mediator r elease from excised human lung tissue with those of steroids. Methods: Human lung tissue was passively sensitized with serum from atopic patients then preincubated with tacrolimus (10(-6), 10(-7), 10(-8) M) or de xamethasone (10(-6) M) for 2 hours. The lung tissue was then exposed to 1.5 mug/mL of mite antigen and then cultured for 48 hours. Culture supernatant s were collected and IL-5 and TNF-cr levels were measured by ELISA. IL-5 an d TNF-alpha messenger ribonucleic acid (mRNA) expression was also investiga ted by reverse transcriptase-polymerase chain reaction. The level of histam ine and leukotriene E4 was also measured in the culture supernatant. In add ition, tryptase staining was performed to compare degranulation of mast cel ls. Results: Antigen stimulation increased histamine and leukotriene release in the supernatant. Tacrolimus significantly and dose-dependently inhibited t he release of histamine and leukotriene; dexamethasone did not. The results of tryptase staining demonstrated that tacrolimus dose-dependently inhibit ed degranulation of mast cells, whereas dexamethasone did not. Antigen stim ulation increased TNF-alpha and IL-5 protein production and mRNA expression . Tacrolimus and dexamethasone significantly inhibited TNF-alpha and IL-5 p rotein production and mRNA expression. Conclusions: Our results indicated that tacrolimus is more powerful in inhi bition of cytokine production and release of chemical mediators than steroi ds, and suggested that this immunosuppressor drug might be useful for the t reatment of asthma.