Genital inflammatory cytokine responses increase HIV risk. Since male partner semen is a complex mixture of immune-modulatory prostaglandins and cytokines, we hypothesized that exposure to semen may influence genital inflammation in women. Here, we investigated cytokine response kinetics of cervical cells following stimulation with seminal plasma from HIV-negative and HIV-positive men characterized as having low or high concentrations of inflammatory cytokines. Irrespective of the HIV status or semen cytokine profile, in vitro stimulation of cervical cells with seminal plasma resulted in significantly elevated concentrations of secreted IL-6, IL-8, TNF-β, MCP-1, GM-CSF, and VEGF within 8 h of stimulation, which tended to decline by 24 h, although this was only significant for TNF-β. Consistent with this, cervical cells responded to seminal plasma with increases in IL-8 and IL-1β mRNA expression of 10-fold. These findings suggest that the impact of semen on local female genital cytokines is likely transient. Although these findings suggest that the impact of semen on local female genital cytokines may not be sustained long-term, this heightened genital inflammation may have implications for HIV risk in women.
While the main reproduction aim of semen is the transport of spermatozoa to the female genital tract, seminal plasma is a complex fluid that also carries a broad array of immunologically active molecules. Seminal plasma has been shown to contain a diverse array of anti-inflammatory and pro-inflammatory soluble mediators that regulate immune responses within the female reproductive tract than can facilitate fertilization. Since the natural inflammatory response to semen deposition in the female genital tract may result in recruitment of activated HIV target cells into the female genital mucosa, we discuss the constituents of semen that may increase the risk for HIV infection in women.
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