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J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):141-9.

Reciprocal regulation of cultured human mast cell cytokine production by IL-4 and IFN-gamma.

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1
Department of Allergy, National Children's Medical Research Center, Tokyo, Japan.

Abstract

BACKGROUND:

T(H)1 and T(H)2 cytokines are thought to regulate allergic inflammation.

OBJECTIVE:

Two key regulatory cytokines, IL-4 and IFN-gamma, were examined for their effects on cytokine production by cultured human mast cells (CHMCs).

METHODS:

CHMCs were obtained by culturing cord blood-derived CD34(+) cells in the presence of stem cell factor and IL-6 for 14 to 16 weeks. CHMCs were passively sensitized with human myeloma IgE and supplemented with or without IL-4 or IFN-gamma. After the sensitization, CHMCs were stimulated with anti-FcepsilonRIalpha mAb. Concentrations of secreted cytokines were measured by using ELISA, and cytokine messenger RNA was analyzed by using quantitative competitive RT-PCR.

RESULTS:

IL-4 profoundly enhanced FcepsilonRI-mediated production of macrophage inflammatory protein (MIP) 1alpha, IL-8, and GM-CSF. For example, the enhancement by IL-4 (10 ng/mL) of the production of MIP-1alpha, IL-8, and GM-CSF was 25-, 7-, and 90-fold, respectively, after 6 hours. IL-4 also enhanced levels of FcepsilonRI-induced cytokine messenger RNA but to a lesser degree. In contrast, IFN-gamma inhibited FcepsilonRI-induced production of MIP-1alpha, IL-8, and GM-CSF. For example, the inhibition by IFN-gamma (10 ng/mL) of FcepsilonRI-mediated production of MIP-1alpha, IL-8, and GM-CSF was 80%, 75%, and 95%, respectively. IFN-gamma also suppressed FcepsilonRI-induced messenger RNA expression of these cytokines. Neither IL-4 nor IFN-gamma affected the kinetics of cytokine production by CHMCs.

CONCLUSION:

These data suggest that IL-4 and IFN-gamma may influence allergic reactions by modulating human mast cell cytokine production.

PMID:
10887317
DOI:
10.1067/mai.2000.107043
[Indexed for MEDLINE]
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