Результаты. В дебюте заболевания установлено статистически значимое снижение уровня лимфоцитов (p<0,001) и их субпопуляций 001),001),001), NK-клеток (<0,001) и Т-лимфоцитов (<0,001)). При этом уровень активированных Т-лимфоцитов был статистически значимо выше (p<0,001) аналогичного показателя в группе контроля. При анализе иммунологических показателей в динамике установлено нарастание общего количества лимфоцитов (p<0,001), Т-лимфоцитов (p=0,003), Т-хелперов (p=0,015); повышенное содержание активированных Т-лимфоцитов (p<0,001) и низкий уровень 001). Показатели фагоцитарного звена у пациентов с COVID-19 в первые дни заболевания были в пределах референсных (аналогичные показатели у лиц контрольной группы). При повторном обследовании (проба 2) отмечено увеличение фагоцитарной активности лейкоцитов и моноцитов (p<0,003 и p<0,09 соответственно). В начале заболевания уже на 4-5-й день болезни в сыворотке крови больных выявляли специфические антитела -IgM и IgG к SARS-CoV-2, ко 2-й неделе заболевания их уровень был достоверно выше, чем при первом исследовании (p<0,009).

The cytokine levels in unstimulated peripheral blood samples differ in relation to age, living conditions (environmental situation, state of medical care, quality of life, etc). Thus, the essential task is to determine normal levels of peripheral blood cytokines for different age groups with respect to regional characteristics. This study aimed to investigate age-associated patterns of the baseline levels for some cytokines in unstimulated peripheral blood samples in healthy children and adults. The studies were carried out at the Laboratory of Clinical Immunology (Clinical and Diagnostic Centre, Yekaterinburg). Peripheral blood samples were taken in 149 healthy children aged from 7 months to 18 years. Group 1 was 7 to 12 months old (29 infants); group 2 was 1 to 3 years old (33 children); group 3 was 4 to 7 years old (29 children); 4th group was 8 to 14 years old (26 children); 5th group, 15 to 18 years old (32 children); and 6th group included 42 adults (19 to 45 years old). The concentrations of TNFα, IFNγ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, and IL-18 in blood serum were determined by common ELISA technique using Vector-Best kits (Novosibirsk, Russia). Analysis of the data made it possible to identify various patterns of age-dependent changes of baseline levels for the determined cytokines: IL-2 showed an increase in concentration by the age of 1-3 years, stable contents up to 18 years, and decreased concentrations in adulthood. IFNγ was at zero levels in children and adolescents, followed by increased levels in adults. IL-4 and IL-6 showed consistently low levels in children and adolescents, with a decrease to zero levels in adult subjects. IL-18, TNFα were at maximal levels at the age of below 7 years followed by a decrease in concentration; IL-1β, IL-17 exhibited bimodal changes, with maximal contents at the age of 1-3 years, and repeated increase in adult age. Nearly stable baseline concentration was noted for IL-10, with a slight increase at 1-3 years, like as for IL-8, with a moderate increase at 15-18 years. For majority of analyzed cytokines, the maximal baseline contents in unstimulated peripheral blood samples were found in children aged 1-3 years.

Varicocele is a varicose dilation of pampiniform plexus veins in testicular gland, considered a special case of phlebopathy. With varicocele, there is impaired venous outflow via the left renal vein from the veins of testicular pampiniform plexus. Increased hydrostatic pressure leads to failure of the wall tone of the testicular vein, valvular venous insufficiency with dilation of the local venous system. Vasodilation requires integrity of endothelial layer, and its damage resulting from hydrodynamic stress is a trigger for development of an inflammatory response and production of cytokines. Pro-inflammatory cytokines have a pronounced damaging effect on endothelial cells, leading to endothelial dysfunction and chronic inflammation. Angiogenesis is an important characteristic of inflammatory disorders. Both inflammation and its controlling mechanisms employ many common factors, including IL-1β, IL-6, IL-8, TNFα. The purposes of our study were: to determine the dynamics of the pro- and anti-inflammatory cytokine levels, and VEGF contents in blood serum of adolescents with left-sided varicocele in order to assess the severity of inflammatory reaction of the vessels in the pampiniform plexus as well as prognosis of angiogenesis and remodeling of the testicular veins. We examined 100 adolescents with left-sided varicocele II-III degree and 30 adolescents without varicocele, who made up the comparison group. All adolescents (14 to 17 years old) underwent determination of IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, VEGF levels in blood serum at a frequency of 1 year, depending on the degree of varicocele, terms after varicocelectomy.Statistically higher levels of pro-inflammatory cytokines were found over different age periods in adolescents with varicocele, as well as increased levels of anti-inflammatory cytokines, which may suggest an inflammatory process in testicular veins associated with varicocele. Higher levels of pro-inflammatory cytokines were found in patients with grade III varicocele compared with patients with grade II condition, but without statistically significant differences. In adolescents prior to varicocelectomy, significantly higher levels of cytokines were determined, which persisted over the postoperative period. Based on these results, one may assume that, in phlebopathy, the inflammatory process persists until surgical correction, and adaptation to the changed blood flow after surgery does not take time. VEGF values remain approximately similar over the observation period, and, probably, the changes of the vessel walls occur due to inflammatory process, and not to activation of angiogenesisIn varicocele disorder, an inflammatory status is observed in the altered testicular venous plexus, being more pronounced in grade III varicocele and affected by subsequent surgical correction.

Varicocele is a vascular disease characterized by abnormal tortuosity and dilation of the veins in pampiniform plexus that drains the testis. Due to difficult outflow of blood via the altered veins, the intratesticular blood flow becomes impaired, leading to pathological changes in the testicular tissue caused by hyperthermia, ischemia, hypoxia and development of inflammatory reaction. Seminal plasma contains numerous proteins, molecules, a wide range of cytokines, chemokines, growth factors. Their properties and levels largely determine the stages of post-testicular maturation of spermatozoa. At the same time, cytokines are an integral part of the inflammatory effect and are synthesized by various immunocompetent cells present in the male reproductive tract. Increased cytokine levels in ejaculate may act as a marker of local inflammatory process, being a significant factor of male infertility. The purpose of our study was to assess cytokine profile of ejaculate in adolescents with varicocele.The level of cytokines IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, VEGF was determined in ejaculate of adolescents aged 17 years. The main group consisted of 100 adolescents with II-III degree varicocele; the comparison group included 30 adolescents without varicocele.Adolescents with varicocele have statistically higher levels of all studied pro-inflammatory cytokines, except of IL-8 and IL-10, which may suggest presence of a local inflammatory process. We did not find significant differences in the levels of cytokines between groups with grade II and III varicocele. However, the levels of pro-inflammatory IL-1β, IL-6 cytokines in ejaculate proved to be increased in the patients with grade III varicocele. When comparing the results between both groups, depending on the period after varicocelectomy and in the comparison group, statistically higher levels of IL-1β, IL-6, TNFα were detected in patients with more recent surgical correction and IL-10 levels in both subgroups with varicocele. This finding, given the progressive course of this disease, may be considered an unfavorable factor, since the pro-inflammatory status of testicular tissue returned, at later terms after surgery.In adolescentswith varicocele, increased levels of pro-inflammatory cytokineswere revealed in the ejaculate. There were no statistically significant differences in the level of cytokines in ejaculate of the patients with II and III degrees of varicocele. At the longer postsurgical period, an increased level of pro-inflammatory cytokines was revealed in the ejaculate samples.