Relationship Between Semen IL-6, IL-33 and Malondialdehyde Generation in Human Seminal Plasma and Spermatozoa

Abstract

Cytokines are physiological seminal components and their abnormal levels, reported in different pathological conditions, negatively influence the sperm function. We analysed the relationship between interleukin (IL)-6 and IL-33 levels and lipid peroxidation (LPO), measured both in semen and sperm lysate, in 44 human semen samples. The semen analysis was performed following the WHO guidelines. Seminal IL-6 and IL-33 concentrations were assessed by ELISA and LPO was evaluated measuring malondialdehyde (MDA) both in seminal plasma and viable spermatozoa. Two small groups of patients with varicocele and infection were extrapolated from the cases analysed and the variables compared with those of a group of control. IL-33 levels were undetectable in all samples and IL-6 levels were positively correlated with both seminal and sperm MDA concentrations (p < 0.01) and negatively with sperm parameters (p < 0.01). Seminal and sperm MDA levels were both negatively correlated with sperm parameters (p < 0.01). IL-6 and semen MDA showed an exponential positive relationship, whereas MDA values measured in viable spermatozoa were low until IL-6 amount reached a concentration of >30 pg/mL, rising consistently. By comparing the variables in the groups, we confirmed that a high IL-6 concentration in the varicocele and infection groups was concomitant with an increase of seminal MDA levels, but also with MDA measured in viable spermatozoa, which represents the novelty of this study. We identified the IL-6 threshold, beyond which sperm MDA concentration rises concomitantly with the increase of IL-6 concentration. Other studies are needed, considering the increasing number of patients with different pathologies affecting male infertility.

Semen microbiota and cytokines of healthy and infertile men

“…Cytokines are physiological seminal components, and their abnormal levels, reported in different pathological conditions, disrupt semen function. 47 Many so-called proinflammatory and immunoregulatory cytokines are produced by testicular somatic and spermatogenic cells, both under normal conditions and in response to inflammatory stimuli. 48 Seminal cytokines are also secreted by immunocompetent cells in various pathogenic conditions, including leukocytospermia.…”

Microbiology and immune mechanisms associated with male infertility

“…showed a positive correlation between IL-6 levels and the level of malondialdehyde (MDA) in semen. The levels of malondialdehyde(MDA) in seminal plasma and semen were negatively correlated with sperm parameters, which further confirmed that IL-6 was involved in oxidative stress induced sperm damage ( 28 ). IL-1α and IL-1β are two forms of IL-1, which are regulators of testicular function, but increased expression of IL-1α and IL-1β in rats with varicocelectic veins, especially in the 11 - and 13-week-old groups, disrupted the balance of inflammation and immunity and had deleterious effects on testicular tissue ( 15 ).…”

Immune regulatory cytokines in seminal plasma of healthy men: A scoping review and analysis of variance

“…IL23 was detected using ELISA technology in two studies, published in 2011 and 2014, and comprising 45 normozoospermic and fertile men (Table 1) at median and mean concentration of 5.9 and 2.2 pg/mL, respectively 75,80 (Figure S2E). IL33 was reported to be undetectable by ELISA in SP from 11 men in a single study published in 2021, including in men with varicocoele and genital infections 112 (Figure S2F, Table 1). One study, published in 2017, reported SP IL37 concentration to be significantly higher in infertile men with varicocoele, compared to healthy fertile men 111 .…”

“…IL33 was reported to be undetectable by ELISA in SP from 11 men in a single study published in 2021, including in men with varicocoele and genital infections 112 (Figure S2F, Table 1). One study, published in 2017, reported SP IL37 concentration to be significantly higher in infertile men with varicocoele, compared to healthy fertile men.…”