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*
Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany;
Department of Dermatology, Albert-Ludwigs-University, Freiburg, Germany; and
Department of Dermatology, Medizinische Hochschule Hannover, Hannover, Germany
The present study assessed the capacity of eosinophils (EOS) to
synthesize the cytokine IL-12. Blood-derived, highly purified human EOS
from six atopic patients and two nonatopic individuals were treated in
culture with IL-4, IL-5, granulocyte-macrophage CSF, IFN-
, TNF-
,
IL-1, RANTES, and complement 5a, respectively. The expression of
both IL-12 protein and mRNAs for the p35 and p40 IL-12 subunits was
strongly induced in all donors by the Th2-like cytokines IL-4 and
granulocyte-macrophage CSF and was also moderately induced by TNF-
and IL-1. IL-5 treatment resulted in IL-12 synthesis in four atopic
donors and one nonatopic donor, whereas IFN- induced IL-12 synthesis
in only two atopic donors. In contrast, RANTES exclusively induced mRNA
for the p40 subunit without detectable protein release, and complement
5a had no effect on IL-12 mRNA or protein expression. EOS-derived IL-12
was biologically active, because supernatants derived from IL-4-treated
EOS superinduced the Con A-induced expression of IFN- by a human
Th1-like T cell line. This activity was neutralized by anti-IL-12
Abs. In conclusion, EOS secrete biologically active IL-12 after
treatment with selected cytokines, which mainly represent the Th2-like
type. Consequently, EOS may promote a switch from Th2-like to Th1-like
immune responses in atopic and parasitic diseases.
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