42 The concentration of PGE prostaglandins in human semen is many times higher than in other areas of the body, and semen contains 19-hydroxy PGE, which is not found elsewhere. The effects of the seminal prostaglandins are two-fold.28,30 First, a cAMP-mediated effect on T cells inhibiting clonal proliferation, as well as natural killer cell function, and biasing CD4 cells to T-helper-2 pattern of cytokine production away from one

favoring a cell-mediated response. Second, PGE is a potent agent inducing a type 2 phenotype in dendritic cells, through its capacity to inhibit IL-12. Hence, at the level of the antigen-presenting cell, PGE and 19-hydroxy PGE alter the balance of cytokines, stimulating IL-10 and inhibiting IL-12 released by these cells, reinforcing CP-868596 in vivo its direct effects and inducing tolerance of antigens that are presented together with the IL-10. While necessary for the survival of the spermatozoa, such tolerance may have adverse effects, in the face of Alectinib in vivo infection. Viruses which can be transmitted in semen (such as HIV & HPV) and other invading organisms would benefit from this switch in cytokines and

the inhibition of the cell-mediated defenses. Not only is the initial immune response affected, but repeated exposure to semen could diminish immune surveillance and the removal of virally infected cells. TGF-beta is now known to be a principal mediator of oral tolerance.26,27 The seminal vesicle is the principal source of TGFβ in rodents, where its synthesis is regulated by testosterone. In contrast, the prostate has been identified as a major site of TGF-beta in men.43 The seminal fluid content of TGF-beta is high, approximately five-fold that of serum and similar to that of colostrum. The normal range for TGF-beta in fertile men has been shown to be approximately 40–150 ng/mL, which remains relatively constant

over time. Upon deposition in the female reproductive tract at coitus, seminal TGF-beta interacts with uterine and cervical epithelial cells, to initiate a cascade of downstream effects.44,45 It has been shown to be a principal agent in Selleck Cobimetinib the post-coital inflammatory response, in mice, resulting in the recruitment and activation of leukocytes, including neutrophils, macrophages, and dendritic cells. Epithelial cells up-regulate expression of several pro-inflammatory cytokines and chemokines within several hours of coitus. In humans, exposure to semen induces neutrophil recruitment into the superficial epithelial layers of the cervix. In addition to preventing aberrant immunity to spermatozoa, seminal fluid components derived from the seminal vesicles have been implicated in inducing an immune response that promotes embryo implantation. Robertson et al.