The relationship between immunosuppressive activity and immunoregulatory cytokines in seminal plasma: influence of sperm autoimmunity and seminal leukocytes.

While the contributions of prostasomes, polyamines and prostaglandins to the immunosuppressive activity (ISA) of human seminal plasma have been well-characterised, the contribution of immunoregulatory cytokines found in seminal plasma has received relatively little attention. Semen samples were collected from adult men displaying normospermic parameters, sperm antibodies or substantially elevated seminal leukocytes. Samples were processed through ultracentrifugation and dialysis (<3500Da) to remove prostasomes, polyamines and prostaglandins, and then assayed for ISA by an in vitro T lymphocyte inhibition assay, as well as by specific immunoassays for transforming growth factor beta(1) (TGFbeta(1)), interleukin-10 (IL-10), activin A and the activin-binding protein, follistatin. Seminal plasma from all groups retained substantial ISA following processing. Compared with normospermic men, this 'large' molecular weight ISA fraction was significantly increased in a subset of men with sperm antibodies, but was not altered in the group with elevated leukocytes. There was no relationship between ISA and any cytokine examined, and only TGFbeta(1) was present at levels sufficient to contribute to ISA. Inhibition with a TGFbeta-specific antibody reduced ISA in seminal plasma by approximately 50%. Across all patients, TGFbeta(1) levels were positively correlated with sperm numbers in the ejaculate and with activin A, but not with follistatin or IL-10. Activin A and IL-10 also displayed a positive relationship, and elevated leukocytes was associated with a significant elevation of IL-10 and activin A, but not TGFbeta(1). It is concluded that 'large' molecular weight molecules, the most important of which appears to be TGFbeta(1), make a significant contribution to immunosuppression by human seminal plasma.