Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men

Abstract

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. 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. 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-beta1 and interleukin (IL)-7, and three chemokines, stromal cell-derived factor-1alpha, 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-1alpha and beta, IL-5, IL-6, IL-13, IL-17, regulated on activation normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1beta, interferon (IFN)-alpha and granulocyte colony-stimulating factor (CSF)], or in a minority of samples (MIP-1alpha, IL-2, IL-10, IL-12, TNF-alpha, IFN-gamma and granulocyte-macrophage-CSF). PMN counts significantly correlated with IL-1beta, IL-6, TNF-alpha, MIP-1alpha, MIP-1beta, IL-13 and IgA concentrations. 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.