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Dihydrotestosterone exerts a depressive influence on the production of
interleukin-4 (IL-4), IL-5, and gamma-interferon, but not IL-2 by activated
murine T cells
BA Araneo, T Dowell, M Diegel and RA Daynes
Division of Cell Biology and Immunology, University of Utah School of
Medicine, Salt Lake City.
The present study examined the effects of the androgen steroid,
dihydrotestosterone (DHT), on murine T-cell production of a number of
lymphokines. Direct exposure of murine T cells to DHT in vitro was found to
reduce the amount of interleukin-4 (IL-4), IL-5, and gamma- interferon
(gamma IFN) produced after activation with anti-CD3 without affecting the
production of IL-2. Exposure of T cells to either androstenedione or
testosterone (the metabolic precursors of DHT) affected no change in the
biosynthesis of either of these lymphokines. We have determined that
macrophages possess 5 alpha-reductase, and are thus competent to metabolize
testosterone to DHT. This physicochemical information is complemented by a
functional analysis of macrophage metabolism of testosterone. By incubating
bone marrow macrophages with testosterone, before their use as accessory
cells, the IL-4 and IL-5 producing potential of the activated T cells
cocultured with them was depressed. That the observed effect was mediated
by the conversion of testosterone to DHT was further corroborated by
illustrating that the inhibition of IL-4 production was abrogated if 4MA, a
specific 5 alpha- reductase inhibitor, was added to macrophage cultures
containing testosterone. The biologic role of DHT in lymphokine and immune
response regulation in vivo was addressed using several lines of
investigation. First, transdermal delivery of DHT to groups of mice altered
the capacity of T cells residing in the draining lymph nodes, only, to
produce lymphokines. Second, treatment of either aged mice or the T cells
isolated from them with a combination of dehydroepiandrosterone and DHT
restored the capacity of their T cells to produce IL-2, IL-4, and gamma IFN
to levels equivalent to that of younger mice. Finally, we observed a
difference between males and females of a given age to produce IL-2, IL-4,
and gamma IFN, with both IL-4 and gamma IFN production being elevated in
females. Collectively, our findings indicate that DHT, similar to other
steroid hormones, may play an important role in lymphokine regulation in
vivo.
Volume 78,
Issue 3,
pp. 688-699,
08/01/1991
Copyright © 1991 by The American Society of Hematology
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