Abstract. The mechanisms of formation of male infertility are increasingly becoming immune-dependent. Immunological isolation of the testes is provided by the anatomical blood-testis barrier and the special tolerance of the immune system to antigens expressed on male gametes. For a better understanding of the immunopathogenetic mechanisms of infertility, a study of the role of various immune factors is required.
The aim: to study the role of pro-inflammatory and anti-inflammatory cytokines in blood serum to clarify their role in spermatogenesis.
Materials and Methods: 45 infertile men aged 22-48 were examined. They were divided into 2 groups: first group – 22 men with a systemic autoimmune disease - rheumatoid arthritis; second group – 23 somatically healthy patients
with idiopathic infertility. The control group included 27 fertile healthy men aged 22-48 years. Determination of the
cytokines concentration in blood serum was carried out by the immunoenzymatic method. Student's t-test was used to compare the significant difference in mean values between groups. P < 0.05 was considered significant.
Results. Patients with autoimmune diseases (rheumatoid arthritis) had the highest rate of leukocytospermia, indicating a possible long-term inflammatory process. In patients with idiopathic infertility, oligozoospermia was diagnosed in 3 patients (13.04%), oligoasthenozoospermia in 7 patients (30.36%), asthenozoospermia in 8 patients (34.78%) and leucocytospermia in 5 patients (21.82%). In patients with rheumatoid arthritis, the concentration of IL-18 (cytokine of the IL-1 family) in the blood serum of infertile men was 1.36 times higher than that of fertile men. The level of IL-6 was 6 times higher, and the concentration of IFN-γ exceeded the norm by more than three times. The level of IL-10 was 9,4 times higher than in control group. Significant changes in the serum cytokine profile were recorded in men with idiopathic infertility. The level of pro-inflammatory cytokines increased statistically significantly: IL-18 – 1.45 times, IL6 – 2.85 times, IFN-γ – 2.65 times. Simultaneously, the level of anti-inflammatory cytokines increased: IL-10 – 3.0 times.
We also analyzed the ratio of serum levels of pro- and anti-inflammatory cytokines. Significant increase in ІL10/TNF-α ratio was recorded in men with idiopathic infertility and infertile men with rheumatoid arthritis. Specifically, in men with idiopathic infertility the ІL-10/TNF-α ratio was 3.3 times higher and in patients with rheumatoid arthritis the ІL-10/TNF-α ratio was 4.1 times higher than in control group. In patients with rheumatoid arthritis the ІL-10/ІFN-γ ratio
was in 3 times higher than in control group. Significant positive correlations were found in healthy fertile men: TGF-β1 – IFN-γ, IL-10 – IL-18 and IL-10 – TNF-α. In men of the control group, the synthesis of IL-18 and TNF-α was balanced by the production of IL-10. The synthesis of IFN-γ was by balanced by the production of TGF-β1.
Conclusions. The development of infertility associated with various accompanying pathologies is related with by changes in both systemic and local immune reactivity. The pro-inflammatory cytokine profile of blood serum and a decrease in the concentration of IL-1β are observed in patients with idiopathic infertility. The largest number of deviations of immune reactivity was found in infertile men with concomitant autoimmune diseases

The mechanisms of formation of male infertility are increasingly becoming immune dependent. This study aims to study the role of pro-inflammatory and anti-inflammatory cytokines in seminal fluid to clarify their role in spermatogenesis. This research is carried out at rheumatology and urology departments of Danylo Halytsky Lviv National Medical University (Ukraine). 45 infertile men aged 22–48 were examined. They were divided into 2 groups: first group – 22 men with a systemic autoimmune disease – rheumatoid arthritis; second group – 23 somatically healthy patients with idiopathic infertility. The control group included 27 fertile healthy men aged 22–48 years. Student's t-test was used to compare the significant difference in mean values between groups. Patients with autoimmune diseases (rheumatoid arthritis) had the highest rate of leukocytospermia, indicating a possible long-term inflammatory process. The TGF-β1 level was higher in men with idiopathic infertility, and in patients with autoimmune pathology was reduced compared to the control group, however these changes were not significant. At the same time in patient of both group the level a pro-inflammatory cytokine IL-18 increased approximately by 2.5 times.
In patients with idiopathic infertility and patients with autoimmune pathology, a simultaneous increase in the IFN-γ level and a decrease in the IL-1β level were found. The ІL-6 level in seminal plasma of infertile men of both groups was increased. The ratio IL-10/TNF-α was decreased in seminal plasma of infertile men with rheumatoid arthritis. It was found that in autoimmune pathology, the increased level of IL-1β in blood serum compared to controls was associated with its reduced level in seminal fluid (r=-0.51, p<0.05). In idiopathic infertility, a low level of IL-1β in seminal fluid was also associated with a low concentration of this cytokine in blood serum (r=0.62, p<0.05). The functioning of the immune and reproductive systems of the male body is closely related and interdependent. Disorders of immune reactivity, which accompany the development of autoimmune pathology associated with disorders of reproductive function in men. The largest number of deviations of immune reactivity was found in infertile men with concomitant autoimmune diseases.