Human Reproduction, Vol 12, 677-681, Copyright © 1997 by Oxford University Press
RW Kelly, GG Carr and HO Critchley
The immunosuppressive activity of human seminal plasma may be one factor in
the aetiology of sexually transmitted disease and could be particularly
important for the spread of human immunodeficiency virus (HIV). The advent
of virus that can preferentially infect Langerhans cells of the genital
mucosa underscores the relevance of seminal plasma effects. Virally
infected cells are eradicated by the killing activity of T cells and
natural killer (NK) cells and this cytotoxicity is stimulated by IL-12
(previously known as natural killer cell stimulatory factor) and partly
inhibited by IL-10 (previously known as cytokine synthesis inhibitory
factor). We have examined the effects of human seminal plasma on the
production of these key cytokines. Cytokine production was measured in
rapidly diluted, fresh, lipopolysaccharide (LPS)-stimulated, whole blood
since this provided leukocytes with minimal exposure to prostaglandin.
Prostaglandin concentrations and cytokine release were measured by ELISA.
Addition of human seminal plasma diluted up to 100,000 times (0.001%) to
blood cell cultures led to a marked increase in the IL-10/IL-12 ratio (P
<0.02). A dose- dependent increase in the ratio was observed in five
separate experiments, from a control value of 1 (no seminal plasma) to a
mean value of 80 (1% seminal plasma). This cytokine switch was also seen
when seminal plasma was substituted by pure prostaglandin E (PGE) and 19-OH
PGE (the main prostaglandin constituent of human seminal plasma).
Lipid-extracted seminal plasma was considerably less active at high
dilutions than whole seminal plasma at the same dilution. However, its
activity could be restored by the addition of synthetic PGE and 19- hydroxy
PGE. A stimulation of IL-10 and a decrease in IL-12 in host- defence cells
of the lower female reproductive tract will seriously affect the ability of
cytotoxic T cells and NK cells to recognise and destroy virally infected
cells. In addition, the stimulation of IL-10 will inhibit the release of
the anti-HIV activity from CD8+ve cells. The cytokine switch reported here,
activated by semen deposition, would exercise a key inhibitory control over
vital immune defences in the lower genital tract, with ablation of
cell-mediated responses and immunosurveillance.
ARTICLES
A cytokine switch induced by human seminal plasma: an immune modulation with implications for sexually transmitted disease
Medical Research Council Reproductive Biology Unit, University of Edinburgh Centre for Reproductive Biology, UK.
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