Cytokines as Potential Diagnostic Markers of Male Infertility

The clinical role of evaluation of cytokines participating in urogenital infections/ inflammations has been recently found to be the important area of interest. The present routine diagnostics of inflammation in the male reproductive tract is mainly based on the determination of leukocyte concentration and microbiological evaluation of the semen. Because the harmful effect of cytokines on spermatozoa is closely connected with the accompanying leukocytospermia, the evaluation of the leukocyte count in the semen still remains an important but insufficient factor to the diagnosis and treatment monitoring of male genital tract infection/inflammation and its particular stages or kinetics. Consideration of additional biomarkers of inflammation, especially in cases of inflammatory conditions which occur without clinical symptoms, seems to be helpful in establishing the proper algorithm [163] . Determination of the levels of proinflammatory cytokines in the seminal plasma using a quantitative immunosorbent test (ELISA) may be one of the basic biochemical markers of the inflammatory process in the ejaculate, at the same time reflecting the inflammatory activity of leukocytes. In multiple studies, the measurement of cytokine concentrations in seminal plasma, such as IL-6 [63, 72, 77], IL-8 [72, 94, 164], IL-18 [71], TNF-a [75, 99], IFN-g [99], IL-2 [68], or sIL-6R [165], can be considered as a potential marker of male infertility caused or complicated by infection/inflammation in the reproductive tract. Data from many independent groups support the need for the examination of IL-6 and IL-8 as excellent markers for early diagnosis of the inflammatory process in the male reproductive system and the rapid initiation of anti-inflammatory treatment before the reproductive potential of the sperm is inhibited [72, 76, 77, 93, 94, 164]. However, other authors reported that the concentration of IL-6 and IL-8 is closely correlated with the number of leukocytes; thus, their determination does not provide any additional information for, e.g., the diagnosis of male accessory gland infection [65, 70, 166].

Numerous reports have appeared in which the limited value of standard semen analysis has been emphasized while assessing males fertilizing potential. Moreover, the number of studies on the clinical significance of the detection of cytokines in the seminal plasma, especially in the context of genital tract infection/inflammation, is increasing. Despite these premises, the measurement of cytokine concentrations is still not a routine clinical practice. Undoubtedly, controlled prospective studies, including a large number of patients, a wide range of analyzed semen parameters, patient characteristics, and their reproductive outcome, are urgently needed to answer the question about the future of the novel biomarkers produced by activated leukocytes, such as granulocyte elastase, proinflammatory cytokines, or ROI secreted to seminal plasma.

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