Hum. Reprod. Advance Access originally published online on September 12, 2007
Human Reproduction 2007 22(11):2928-2935; doi:10.1093/humrep/dem281
Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men
1 Fearing Research Laboratory, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 2 Department of Obstetrics and Gynecology, Division of Reproductive Biology, Boston University School of Medicine, Boston, MA, USA
3 Correspondence address. Department of Obstetrics and Gynecology, Division of Reproductive Biology, School of Medicine, Boston University, 670 Albany Street, Suite 515, Boston, MA 02118, USA. Tel: +1-617-414-8486; Fax: +1-617-414-8481; E-mail: joseph.politch{at}bmc.org
BACKGROUND: The purpose of this study was to establish normal reference values for several immunologic factors in semen to provide a foundation for understanding their physiologic significance in health and disease.
METHODS: Semen from 83 healthy, fertile men was assessed by Bio-Plex or enzyme-linked immunosorbent assay to determine quantities of immunoglobulin (Ig) isotypes, chemokines, cytokines and growth factors. We also enumerated polymorphonuclear granulocytes (PMN) by peroxidase staining to examine the association of inflammation with levels of these factors.
RESULTS: High concentrations of IgG and IgA were detected in all samples. IgG concentrations were significantly higher than IgA concentrations (P < 0.0001). Likewise, two multifunctional growth factors, transforming growth factor-β1 and interleukin (IL)-7, and three chemokines, stromal cell-derived factor-1
, monocyte chemotactic/chemoattractant protein-1 and IL-8, were present in high concentrations in all samples (medians >1000 pg/ml). Other soluble factors were detectable in low concentration (medians <150 pg/ml), either in a majority of samples [IL-1 and β, IL-5, IL-6, IL-13, IL-17, regulated on activation normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1β, interferon (IFN)- and granulocyte colony-stimulating factor (CSF)], or in a minority of samples (MIP-1, IL-2, IL-10, IL-12, TNF-, IFN-
and granulocyte-macrophage-CSF). PMN counts significantly correlated with IL-1β, IL-6, TNF-, MIP-1, MIP-1β, IL-13 and IgA concentrations.
CONCLUSIONS: The semen of healthy, fertile men contains a broad array of immunologic factors. These normative values can serve as a foundation for future studies on the role of these factors in infertility, genital tract infections and other pathologic conditions.
Key words: semen/cytokines/chemokines/immunoglobulins/polymorphonuclear granulocytes
Submitted on June 12, 2007; resubmitted on August 1, 2007; accepted on August 16, 2007.
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