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.

Case of parvovirus B19 infection and immunodeficiency in the patient with Gilbert syndrome

A case of long-term persistence of parvovirus B19 is described for the first time in a patient with Gilbert's syndrome against the background of immunodeficiency with predominance of infectious symptoms (chronic herpesvirus infection). Previously, the patient (male, 48 years old) was diagnosed with Gilbert's syndrome, chronic rhinosinusopharyngitis, and chronic herpesvirus infection. In July 2017, parvovirus B19 DNA was detected in blood. No clinical manifestations of infectious erythema were noted. The patient was admitted to the medical center of St. Petersburg Pasteur Institute. His blood samples obtained under informed consent were examined at the medical center in Central Clinical and Diagnostic Laboratory of St. Petersburg Pasteur Institute in January and June 2018 and in November 2019. ELISA test systems “Anti-Parvovirus B19 ELISA (IgM)” and “Anti-Parvovirus B19 ELISA (IgG)” (Euroimmune, Germany), as well PCR reagent kit “AmpliSens Parvovirus B19-FL” (FSB Central Research Institute of Epidemiology of Rospotrebnadzor, Russia) were used for specific diagnostics. Interferon status was determined by the induced production of IFN types I, II and circulating (serum) interferons. Moreover, we considered the laboratory data obtained earlier at different medical facilities of St. Petersburg. IgM class antibodies to the parvovirus B19 were not detected in the blood samples obtained in 2018. IgG antibody titer was 96 IU/ml and 264 IU /ml, respectively. Parvovirus B19 DNA was isolated from blood plasma, but the viral load was less than 720 IU of PVB19 DNA/ml (1.5 x 102 and 1.9 x 102 copies of DNA/ml, respectively). Clinical blood analysis, showed only minor (no more than 7%) deviations from the reference values, increased hemoglobin saturation of red blood cells (RBC), a decreased width of RBC distribution curve, and relative lymphocytosis. A deficiency of various interferon types was revealed: IFNγ level was 80 IU/ml in both samples, IFNα, IFNβ amounts varied from 80 to 160 IU/ml, respectively. The period of parvovirus B19 DNA persistence in blood was 11 months in presence of immunodeficiency. The patient was administered drugs of the interferon group. Parvovirus B19 DNA was not detected in clinical samples of November 2019; IFNα, IFNβ and IFNγ values were 160 IU/ml. We have detected recovery of lymphoid cell ratio, increase in their number, and improved indexes of interferon status.

EXPERIENCE OF IMMUNOCORRECTIVE TREATMENT IN THE MANAGEMENT OF PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA ON THE BACKGROUND OF GENITAL PAPILLOMAVIRUS INFECTION

Introduction. Human papillomavirus (HPV), its highly oncogenic types, is considered to be the initiating factor in the development of dysplasia and cervical cancer The role of immunomodulatory therapy in reducing the risk of cervical cancer in women with cervical intraepithelial neoplasia (CIN) associated with HPV infection remains in the focus of researchers. Aim of the study: to evaluate the effectiveness of the use of the immunomodulator Allokin-alfa in the complex treatment of cervical intraepithelial neoplasia against the background of genital papillomavirus infection. Materials and methods. We examined 60 women who received CIN1- 2 treatment on the background of HPV infection of high oncogenic risk in the multidisciplinary medical center of the Odessa National Medical University. The patients were divided into 2 groups: 1 (main) group consisted of 30 women who received cold plasma ablation of cervical dysplasia in combination with immunomodulatory therapy with alloferon, group 2 (comparison) consisted of 30 patients who received standard cold plasma ablative treatment without immunomodulators. The control group consisted of 30 healthy women. All women underwent cytomorphological examination of the cervical epithelium, HPV testing, colposcopy, and targeted biopsy. Immunological status was assessed by indicators of cellular and humoral immunity, the content of α- and γ-interferon. Results. In patients with CIN1-2 against the background of HPV, an increase in the level of serum Ig A, CD8 level, a decrease in the CD4 content and immunoregulatory index, CD19 content were revealed, which indicated immunosuppression. Immunocorrective therapy witn alloferon (Allokin-alfa) in complex, with cold plasma ablation, treatment of CIN1-2 promoted the normalization of the parameters of immunity and interferon status, which contributed to the acceleration of epithelialization, (OR — 15,48; 95% CІ: 2,05-136,45; р=0,0094). a decrease in the frequency of residual lesions, and a HPV elimination. Conclusions. Complex treatment of CIN1-2 using cold plasma ablation and immunocorrection by perioperative administration of alloferon (Allokin-alfa) is accompanied by better functional results, compared only with the use of cold plasma ablation: accelerated epithelialization, improved colposcopic picture, decreased frequency of relapses, elimination of HPV, normalization of immunе and interferon status.

INTERFERON STATUS OF ENDOMETRY IN PATIENTS WITH MISCARRIAGE AND “THIN ENDOMETRY” SYNDROME

The article presents the results of examination of 21 patients with miscarriage and “thin endometry” syndrome compared with 20 patients without reproductive losses and the presence of normal endometrial thickness. Interferon gamma intracellular production by cytotoxic endometrial lymphocytes was investigated by flow cytofluorometry. Based on the study, it was found that in patients with miscarriage and “thin endometry” syndrome, the interferon gamma intracellular production by cytotoxic CD8+ lymphocytes was sharply suppressed by almost 36 times, by CD56+ lymphocytes - by 13 times, by CD16+ lymphocytes - by 4.5 times.

Effect of vitamin D and interferon α-2b on cytokine profile in pregnant women with vaginal infections

A study was conducted to evaluate effectiveness of vitamin D and interferon α-2b preparations on cytokine profile in pregnant women with vaginal infections. It was shown that pregnant women with vs. without bacterial vaginosis were featured with low vitamin D level in 53.8–60.5% cases. Administration of vitamin D and interferon α-2b preparations in combination with antibacterial therapy in pregnant women with bacterial vaginosis conferred anti-inflammatory effect resulting in normalized IL-8 level corresponding to that one in healthy subjects. Use of vitamin D altered interferon status and augmented antimicrobial activity in pregnant women confirmed by reduced rate of ARI episodes.

The effect of Esberitox on the functional activity of 2D-positive natural killer cells (NKG2D) and interferon status in patients with recurrence of herpes simplex virus infection

The aim of the study was to assess changes in the functional activity of 2D-positive natural killer cells (NKG2D) and interferon status in patients with recurrence of herpes virus infection under the influence of Esberitox.Materials and methods. We studied 30 patients aged 22-45 years old with frequent relapsing labial herpes, previously verified by PCR. The frequency ofexacerbations at the time of the study was 6 (5.3 ± 1.4) and more than once a year. Patients were initially examined within 24 hours of the appearance of rashes.The expression of CD314 on the surface of CD3-CD56 lymphocytes was determined by flow cytometry(EPICS XL, Beckman Coulter). The content of cytokines (α-and γ-IFN) in supernatants was determined by enzyme immunoassay (IBL, Germany). Patients took Esberitox tablets, 2 tablets x 3 times a day, and daily1-gram tablets of Valacyclovir for 7 days. The control group consisted of 10 patients receiving only tablet valacyclovir.Results. As a result of the study, it was found that the final leveling of symptoms with combined treatment with Esberitox was noted by the end of 5-6 days, with basic treatment - by 9-10 days. There was a decrease in the relapse rate (3 patients) during the observation period within 2 months after the end of the course of treatment.In patients receiving basic Valacyclovir therapy, relapses during the observation period were recorded in more than half of the examined individuals (6 patients). The positive dynamics of the increase in the level of γ-IFN and α-IFN in patients of the main group and itsalmost absence in the control group were established.The dynamics of surface expression of the NKG2D receptor on peripheral blood NK cells showed an increase parameters under the influence of the Esberitox drug compared with Valacyclovir monotherapy, with no significant changes in other lymphocyte subpopulations. Conclusions. The administration of Esberitox in case of frequently recurring herpes virus infection is a promising method of combined immuno-adaptive therapy, which requires further careful study.

Rational therapy for acute respiratory infections in young children with recombinant interferon alfa-2b

Influenza and acute respiratory viral infections (ARVI) remain a global health problem worldwide, and therefore the search for effective means of prevention and treatment of these diseases is extremely urgent. Objective. To evaluate the therapeutic efficacy and safety of a drug form of recombinant human IFN alpha-2b in combination with a complex of antioxidants (Viferon®-suppositories) in children with ARVI. Patients and methods. Clinical and laboratory studies were conducted in 100 children (toddlers up to 3 years old), hospitalized in St. Olga's children hospital No 4 with a diagnosis of influenza or ARVI. The etiology of diseases was established using serological methods and immunofluorescence analysis; the immune and interferon status was determined. VIFERON®-suppositories were used rectally daily in age-related dosages. The effectiveness of therapy was evaluated by comparative analysis of disease symptoms, as well as laboratory indicators – immune and interferon status. Results. The use of VIFERON® – suppositories contributed to reducing intoxication and catarrhal symptoms, speeding up the recovery time of patients. After the treatment, the children's ability to produce IFN-α and – γ, as well, as sIgA content in nasal secretions, increased, but there was no marked enhancement in serum IL-1β, IL-8 levels, whereas the children in the control group and in 30% of cases occurred to change them. The use of the medicine did not cause any complaints in patients and staff. Conclusion. Data from clinical and laboratory studies of children hospitalized for ARVI, whose therapy included the VIFERON® – suppositories, indicate a significant therapeutic effect of this medicine and restoration of the immune and interferon defense systems of patients. Keywords: children, acute respiratory viral infections, recombinant interferon α-2b, immune status, interferon status, antiviral therapy, cytokines IL-1β, IL-8, IL-10, TNF-α