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


CONCLUSIONS
These data suggest that IL-4 and IFN-gamma may influence allergic reactions by modulating human mast cell cytokine production.
Tachimoto
H
H
Department of Allergy, National Children's Medical Research Center, Tokyo, Japan.
Ebisawa
M
M
Hasegawa
T
T
Kashiwabara
T
T
Ra
C
C
Bochner
B S
BS
Miura
K
K
Saito
H
H
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D017455:Receptors, IgE; D015847:Interleukin-4; D007371:Interferon-gamma