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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2668-2671
RAPID COMMUNICATION
Divergent Effects of Interleukin-4 and Interferon- on
Macrophage-Derived Chemokine Production: An Amplification Circuit of
Polarized T Helper 2 Responses
Raffaella Bonecchi,
Silvano Sozzani,
Johnny T. Stine,
Walter Luini,
Giovanna D'Amico,
Paola Allavena,
David Chantry, and
Alberto Mantovani
From the Istituto di Ricerche Farmacologiche "Mario Negri,"
Milan, Italy; the ICOS Corp, Bothell, WA; and the Department of
Biotechnology, Section of General Pathology, Università di
Brescia, Brescia, Italy.
Macrophage-derived chemokine (MDC) is a CC chemokine that recognizes
the CCR4 receptor and is selective for T helper 2 (Th2) versus T helper
1 (Th1) cells. The present study was designed to investigate the effect
of the prototypic Th2/Th1 cytokines, interleukin-4 (IL-4) and
interferon- (IFN-), on the production of MDC by human monocytes.
IL-4 and IL-13 caused a time-dependent (plateau at 24 hours) and
concentration-dependent (EC50 2 and 10 ng/mL, respectively)
increase of MDC mRNA levels in monocytes. Increased expression of MDC
mRNA was associated with protein release in the supernatant. MDC
expression and production induced by IL-4 and IL-13 were inhibited by
IFN-. IFN- also suppressed the constitutive expression of MDC in
mature macrophages and dendritic cells. These results delineate an
amplification loop of polarized Th2 responses based on differential
regulation of MDC production by IL-4 and IL-13 versus IFN- and on
the selectivity of this chemokine for polarized Th2 cells.
© 1998 by The American Society of Hematology.
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