Hormone therapy affecting interferon defense in children with infectious mononucleosis

23 children diagnosed with acute infectious mononucleosis were hospitalized and examined after a short prednisolone treatment course. Related interferon status during infection was compared with that in 38 patients with acute infectious mononucleosis receiving no hormone therapy. Interferon status was investigated by Ershov method, allowing to estimate amount of interferon in the blood serum samples or patient blood cell culture by assessing interferon biological activity. Along with measuring IFNα or IFNγ biological activity, their level was quantified by using enzyme immunoassay. Immunological examination conducted on the next day after the end of hormone therapy revealed sharply decreased potential of patient blood cells to produce both IFNα and IFNγ. The multiplicity of IFNα and IFNγ titer reduction in various patients varied by 4–5 and 3–4-fold, respectively. The concentration of IFNα, determined by ELISA, decreased by 4–6-fold, whereas for IFNγ — by 1.5–2-fold. A follow-up examination 1 month after discharge from the clinic showed that mean IFNα titer in children aged 3–6 years and treated with prednisolone was significantly reduced compared to the baseline, whereas most patients receiving no hormone therapy had normal IFNα production. The change in the level of IFNα 1 month after hormone therapy in 7–14-year age group was similar. IFNγ production quickly recovered, and 1 month after discharge from the clinic, its concentration in culture supernatants from patients reached 10–15 ng/ml, exceeding normal values more than twice. The biological activity of IFNγ in these culture supernatants was significantly higher than those immediately after hormone therapy, whereas in 3–6-year-old group of patients it was also higher than baseline level. These results can serve as a laboratory justification for including recombinant IFNα-2b drugs in the therapy of such patients, presumably immediately after the end of hormone course. Overall, laboratory justified administration of interferon preparations seems to be necessary to determine optimal timepoint for applying such drugs to increase effectiveness for achieving a durable patient recovery

Phage therapy in antibiotic resistant pneumonia: immunomodulation or redistribution?

Our report concerns the observations made during the treatment of pneumonia with individually selected bacteriophages in HCAI patients on mechanical ventilation. 19 patients on mechanical ventilation whose condition was complicated by antibiotic-resistant pneumonia were examined. The treatment of patients was supplemented with phage therapy, bacteriophages were selected individually for each patient, taking into account the microbial etiology of the disease (Pseudomonas aeruginosa, Кlebsiella pneumoniae, Acinetobacter baumanii). Immunophenotyping of blood lymphocytes was carried out using 2-3-parameter flow cytometry. The functional activity of blood leukocytes was assessed by their ability to produce IFNα and IFNγ during cultivation. The level of interferons production in supernatants collected after cultivation was quantitatively evaluated both by their concentration (ELISA, reagents from “Vector-Best-Europe”, Russia) and by their biological activity. Statistical processing of the results was carried out using the Statistica 6 program according to the nonparametric Mann-Whitney U-test. In the course of successful phage therapy with individually selected bacteriophages overcoming of lymphopenia (if there was one) and an increase in both the number and functional activity of peripheral blood lymphocytes in all patients with pneumonia observed are noted. The relationship between the microbial load (mono- or mixed infection, the number of CFU pathogens of pneumonia, the need for repeated courses of phage therapy) and the degree of deficiency in one or another subpopulation of lymphocytes was not detected. Activation of the immune system achieved after one course of phage therapy was maintained for at least 3 weeks after phage administration was discontinued

КЛИНИКО-ИММУНОЛОГИЧЕСКИЕ ОСОБЕННОСТИ СОЧЕТАННОГО ТЕЧЕНИЯ КОКЛЮША И ХЛАМИДИЙНОЙ ИНФЕКЦИИ У ДЕТЕЙ

The article presents the analysis of clinical and immunological features of the combined course of pertussis and respiratory chlamydia in children. The study of the prodromal period and spasmodic cough symptoms showed that concomitant chlamydial infection did not significantly affect the severity of pertussis: 63.2% of patients had mild degree and 36.8% — moderate severity of the disease. However, in this case, the disease was delayed. Bronchitis and in some cases obstructive bronchitis was observed mainly in children under 1 year.The study of the lymphocytes subpopulation found that the content of NK cells decreased only in 10.5% of children, T helpers — in 21.1%, the ratio of CD4+ /CD8+ — in 26.3%. The function of cytokine network was characterized by more active production of such proinflammatory cytokines as IFN and TNF than their production during pertussis monoinfection. The levels of production of IL-8 and IL-6 were similar in all the studied groups. The production of IL-4 by lymphocytes in children with whooping cough in combination  with chlamydial infection was weaker then in patients with pertussis monoinfection  or in healthy children. These features are considered as immunological predictors of long reconvalescence in patients with association of pertussis and respiratory chlamydia.Представлен анализ клинико-иммунологических особенностей сочетанного течения коклюша и респираторного хламидиоза у детей. Изучение симптомокомплекса продромального периода и спазматического кашля показало, что сопутствующая хламидийная инфекция не оказывает существенного влияния на тяжесть течения основного  заболевания: у 63,2% больных наблюдались лёгкие, у 36,8% — среднетяжёлые формы болезни. Вместе с тем имело место затягивание выздоровления. Развитие бронхитов было характерно преимущественно  для детей в возрасте до 1 года, с развитием обструктивного синдрома в некоторых случаях.При исследовании субпопуляционного состава лимфоцитов установлено,  что у 10,5% детей было снижено содержание NK-клеток, содержание Т-хелперов — у 21,1%, соотношение CD4+/CD8+ — у 26,3%. Для функционирования цитокиновой сети была характерна активная продукция таких провоспалительных цитокинов, как ИФН и ФНО. Наряду с этим выявлены низкие показатели продукции ИЛ-8, ИЛ-6 и ИЛ-4, что позволяет расценивать их как неблагоприятные иммунологические пре-дикторы затяжного течения заболевания у больных коклюшем при сочетании с респираторным хламидиозом

Age-related aspects of cytokine profile of immune response in children with pertussis

The article presents a comparative analysis of the cytokine network in 161 patients with pertussis under the age of 1 year and in 180 patients over the age of 1 year. The studies revealed lower production of immunoregulatory cytokines (interferon-γ and interleukin-2) in patients under the age of 1 year at all stages of the disease and with all variants of pertussis (both mono- and mixed infections). The researchers revealed the relationship between the level of interferon-γ production and the severity of pertussis. They revealed age differences in the interferon-8 production in patients with mixed infection, which can determine clinical features and cause bronchopulmonary complications. The authors demonstrated the features of the dynamics of spontaneous and induced production of interleukin-6 and anti-inflammatory cytokines (interleukin-4, interleukin-10) in children under the age of 1 year; these features can be considered as immunological markers determining the imperfection of the humoral response in patients with pertussis in this age group

CLINICAL AND IMMUNOLOGICAL FEATURES OF THE COMBINED COURSE OF PERTUSSIS AND CHLAMIDYAL INFECTION IN CHILDREN

The article presents the analysis of clinical and immunological features of the combined course of pertussis and respiratory chlamydia in children. The study of the prodromal period and spasmodic cough symptoms showed that concomitant chlamydial infection did not significantly affect the severity of pertussis: 63.2% of patients had mild degree and 36.8% — moderate severity of the disease. However, in this case, the disease was delayed. Bronchitis and in some cases obstructive bronchitis was observed mainly in children under 1 year.The study of the lymphocytes subpopulation found that the content of NK cells decreased only in 10.5% of children, T helpers — in 21.1%, the ratio of CD4+ /CD8+ — in 26.3%. The function of cytokine network was characterized by more active production of such proinflammatory cytokines as IFN and TNF than their production during pertussis monoinfection. The levels of production of IL-8 and IL-6 were similar in all the studied groups. The production of IL-4 by lymphocytes in children with whooping cough in combination  with chlamydial infection was weaker then in patients with pertussis monoinfection  or in healthy children. These features are considered as immunological predictors of long reconvalescence in patients with association of pertussis and respiratory chlamydia

КЛИНИКО-ИММУНОЛОГИЧЕСКИЕ ОСОБЕННОСТИ СОЧЕТАННОГО ТЕЧЕНИЯ КОКЛЮША И ХЛАМИДИЙНОЙ ИНФЕКЦИИ У ДЕТЕЙ

The article presents the analysis of clinical and immunological features of the combined course of pertussis and respiratory chlamydia in children. The study of the prodromal period and spasmodic cough symptoms showed that concomitant chlamydial infection did not significantly affect the severity of pertussis: 63.2% of patients had mild degree and 36.8% — moderate severity of the disease. However, in this case, the disease was delayed. Bronchitis and in some cases obstructive bronchitis was observed mainly in children under 1 year.The study of the lymphocytes subpopulation found that the content of NK cells decreased only in 10.5% of children, T helpers — in 21.1%, the ratio of CD4+ /CD8+ — in 26.3%. The function of cytokine network was characterized by more active production of such proinflammatory cytokines as IFN and TNF than their production during pertussis monoinfection. The levels of production of IL-8 and IL-6 were similar in all the studied groups. The production of IL-4 by lymphocytes in children with whooping cough in combination  with chlamydial infection was weaker then in patients with pertussis monoinfection  or in healthy children. These features are considered as immunological predictors of long reconvalescence in patients with association of pertussis and respiratory chlamydia.Представлен анализ клинико-иммунологических особенностей сочетанного течения коклюша и респираторного хламидиоза у детей. Изучение симптомокомплекса продромального периода и спазматического кашля показало, что сопутствующая хламидийная инфекция не оказывает существенного влияния на тяжесть течения основного  заболевания: у 63,2% больных наблюдались лёгкие, у 36,8% — среднетяжёлые формы болезни. Вместе с тем имело место затягивание выздоровления. Развитие бронхитов было характерно преимущественно  для детей в возрасте до 1 года, с развитием обструктивного синдрома в некоторых случаях.При исследовании субпопуляционного состава лимфоцитов установлено,  что у 10,5% детей было снижено содержание NK-клеток, содержание Т-хелперов — у 21,1%, соотношение CD4+/CD8+ — у 26,3%. Для функционирования цитокиновой сети была характерна активная продукция таких провоспалительных цитокинов, как ИФН и ФНО. Наряду с этим выявлены низкие показатели продукции ИЛ-8, ИЛ-6 и ИЛ-4, что позволяет расценивать их как неблагоприятные иммунологические пре-дикторы затяжного течения заболевания у больных коклюшем при сочетании с респираторным хламидиозом.</p