The Role of Cytokines in Semen Inflammation

The activation of leukocytes at a site of the inflammatory process is strictly connected with both the oxidative burst and the initiation of an immune response directed against an infectious agent. The secretion of cytokines is one of the first signals from the innate host defense to combat inflammation. Proinflammatory cytokines are one of the mediators of the host response to inflammatory reaction. Generated by both the cells of the immune system as well as those of surrounding tissues in response to external stimuli, inflicted injury, or other cytokines, they modulate inflammatory reactions, acting as the regulatory factors in different biologic processes [84] . In literature, proinflammatory cytokines have not always correlated with the presence of bacterial agents in the semen. In some reports, seminal plasma cytokine concentrations were similar investigating samples from culture-positive and culture-negative males [72, 123]. However, in most studies regarding male genital infection/inflammation, cytokines and various soluble receptors of immunoregulatory cytokines have been expressed distinctly in the seminal plasma [71, 93, 94, 124]. Moreover, some authors reported that the concentration of some of these factors was elevated in men with pyospermia and additionally correlated with the elastase activity of polymor-phonuclear white blood cells [77]. It is well known that cytokine participation in inflammation is closely connected with the accompanying leukocytospermia [57, 100, 104]. Leukocytes in the semen are the major source of ROI, and ROI production by these cells is enhanced by bacterial products or cytokines [99],

Based on the presence of bacteria and/or leukocytes in the semen, the kinetics of the inflammatory process in the male urogenital tract was studied in situ [85, 125] (Fig. 9.4). The infiltration of an infectious factor to the male reproductive system leads to migration and activation of leukocytes, mostly phagocytic cells. In the course of the inflammatory process, the excessive production of ROI and the activation of appropriate receptors and signal transduction pathways provide biologically active substances, such as proteases and inflammatory cytokines, at the same time. The released proinflammatory cytokines are the next mediators of the host response to infection/inflammation which together with ROI modulate the activities of the prooxidative and antioxidative systems to the advantage of the ROI burst. It has been suggested that the reduced total antioxidant capacity (TAC) of the seminal plasma cannot be sufficient to ensure sperm quality [126, 127]. The consequence of the locally produced mediators in the inflammatory reaction is a permanent peroxi-dative damage to spermatozoa and their biological function. Literature on the subject also suggests that the remnants of oxidative stress in the semen may be maintained over a long period of time, even after the infectious factor has been eliminated, and that the effects of oxidative stress accompanying genital tract inflammation (reflected by leukocytospermia) on sperm parameters might be strictly dependent on the initial antioxidant capacity. In this context, the time needed for restoring oxidative balance in semen is longer in cases of men who are infertile at the start of inflammation [85] .

In spite of the fact that the semen consists of spermatozoa subpopulations with different fertilizing potential, the oxidative stress with its consequences on sperm structures can lead to a damage of sperm biological function. Most probably, the crucial role in perpetuation of the inflammatory process in the semen may belong to cytokines and for this reason these bioactive substances may constitute an important link between inflammation and male infertility [76]. The local activity of the bioac-tive substances released through leukocytes during the inflammatory reaction and

Fertilization Oxidative Stress

Fig. 9.4 Kinetics of inflammatory process in semen. Relationship between cytokines and oxidative stress. Bacterial invasion (phase I) or local tissue damage is accompanied by infiltrating phagocytic and mononuclear cells (phase II) connected with the production and release of large amounts of ROS and proinflammatory cytokines (phase III). The cytokines may modulate the activities of the prooxidative and antioxidative systems which also may bring enhanced secretion of ROS (phase IV). When the amount of ROS exceeds the potential of the antioxidative defense, peroxidative damage to sperm occurs, which in turn may lead to sperm dysfunction that results in fertility problems

Fig. 9.4 Kinetics of inflammatory process in semen. Relationship between cytokines and oxidative stress. Bacterial invasion (phase I) or local tissue damage is accompanied by infiltrating phagocytic and mononuclear cells (phase II) connected with the production and release of large amounts of ROS and proinflammatory cytokines (phase III). The cytokines may modulate the activities of the prooxidative and antioxidative systems which also may bring enhanced secretion of ROS (phase IV). When the amount of ROS exceeds the potential of the antioxidative defense, peroxidative damage to sperm occurs, which in turn may lead to sperm dysfunction that results in fertility problems reciprocal interactions among the particular inflammatory mediators (bacteria, leukocytes, proinflammatory cytokines) is an interesting subject, which has recently been often taken up and which has direct clinical implications. Creation of a model for in vitro inflammatory conditions enables observations of particular mediators of inflammatory reaction and their influence on the qualitative and quantitative changes in the oxygen metabolism of the semen which, in consequence, determine the intensity of toxic interactions among oxygen metabolites and the macromolecules, such as lipids, proteins, and DNA, what obviously cannot be traced in a healthy or a sick patient in in situ conditions.

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

Get My Free Ebook


Post a comment