Rw. Kelly et al., A CYTOKINE SWITCH INDUCED BY HUMAN SEMINAL PLASMA - AN IMMUNE MODULATION WITH IMPLICATIONS FOR SEXUALLY-TRANSMITTED DISEASE, Human reproduction, 12(4), 1997, pp. 677-681
The immunosuppressive activity of human seminal plasma may be one fact
or in the aetiology of sexually transmitted disease and could be parti
cularly 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 effe
cts, Virally infected cells are eradicated by the killing activity of
T cells and natural killer (NK) cells and this cytotoxicity is stimula
ted by IL-12 (previously known as natural killer cell stimulatory fact
or) and partly inhibited by IL-10 (previously known as cytokine synthe
sis inhibitory factor), We have examined the effects of human seminal
plasma on the production of these key cytokines, Cytokine production w
as measured in rapidly diluted, fresh, lipopolysaccharide (LPS)-stimul
ated, whole blood since this provided leukocytes with minimal exposure
to prostaglandin, Prostaglandin concentrations and cytokine release w
ere 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), Th
is cytokine switch was also seen when seminal plasma was substituted b
y pure prostaglandin E (PGE) and 19-OH PGE (the main prostaglandin con
stituent of human seminal plasma), Lipid-extracted seminal plasma was
considerably less active at high dilutions than whole seminal plasma a
t the same dilution, However, its activity could be restored by the ad
dition 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-reprodu
ctive 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 ac
tivity from CD8+ve cells, The cytokine switch reported here, activated
by semen deposition, would exercise a key inhibitory control over vit
al immune defences in the lower genital tract, with ablation of cell-m
ediated responses and immunosurveillance. (C) European Society for Hum
an Reproduction and Embryology.