[Human interferon modulates infected vascular endothelium function].

BACKGROUND: To study impact of interferon (IFN) alpha, beta and gamma on the Herpes simplex virus type 1 (HSV-1) infected endothelial cells functional activity related with participation in the inflammation development. MATERIALS AND METHODS: In the work endothelial cells isolated from umbilical vein were used. Intact and infected cultures were treated by interferon and in the dynamics of cultivation tested mediators in the cultural medium. RESULTS: All investigated interferons activated the production of IL-6. IFN alpha, beta activated the production of IL-8, while IFN gamma inhibited her. IFN alpha and gamma increased synthesis of nitrogen oxides and reduced the synthesis of endothelin-1, while IFN beta activated the production of endothelin-1. CONCLUSION: Infection of endothelial cells isolated from umbilical vein with HSV-1 does not alter the ability of interferon in modulating of proinflammatory cytokines, nitric oxide and endothelin-1 synthesis. It is obvious in the body modulation manifestations of innate immunity under the influence of exogenous interferon is implemented both intact and infected with HSV-1-vascular endothelium and nature modulation is determined by the type of IFN.

[Adhesion molecules expressed in vascular endothelial cells in natural immunity against viral infections].

Cell adhesion molecules (CAM) expressed in vascular endothelium ensure integrity of the endothelial layer, recruitment and transmigration of leukocytes. Being receptors of many viruses, they play a role in immune control and infectious processes. Monoclonal anti-ICAM-1 antibodies enhance infection of primary human umbilical vein endothelial cell (HUVEC) cultures with HIV-1 due to incorporation into virions. IFN-gamma activates expression of ICAM-1 on HIV-infected HUVEC and thereby promotes binding of this molecule to complementary molecules on a greater number of sensitive cells, virion transfer onto them, and broad dissemination of the virus. Recombinant human IFN-alpha, IFN-beta and IFN-gamma influence (activate, inhibit) CAM shedding from HUVEC both intact and infected wit HSV-1. Activated shedding in the blood stream due to competition between soluble and endothelial CAM slows down recruitment and transmigration of leukocytes, i.e. regulates inflammation. CAM incorporated in microparticles can influence a wide spectrum of pathological processes Endothelial CAM may be a target for the delivery of pharmaceuticals for the treatment of vascular (including infectious) pathology.

[The effects of the microbial components of the probiotic Acilact on the cell-mediated immunity factors under experimental conditions].

The authors analyzed the effects of the microbial components of the probiotic Acilact on the cell-mediated factors of the immune homeostasis. According to the results, L. acidophilis stimulates the functional activity of immunocompetent cells, especially T-cell mediated immunity with strain- and dose-depending differences in intensity. The study demonstrated the ability of L. acidophilis to activate expression of the genes of pro-inflammatory cytokines (IFNgamma, IL-6, 12, and TNFalpha), to induce production of IFNalpha and IFNgamma, and increase interferon production, with additional stimulation of lymphoid organ cells with specific inductors in vitro. The study established that L. acidophilis stimulates production of macrophage migration inhibition factor by immunocompetent cells of Peyer's plaques and the splen, and induces its quantitative increase in the serum of CBA mice. The study detected immunocorrecting effect of L. acidophilis by the example of experimental shigellous infection, demonstrated intensification of the prolipherative activity of immunocompetent T-cells, induction of the expression of the genes of pro-inflammatory cytokines (IFNgamma, IL-1beta, 6, 12, and TNFalpha), but not IL4 and 10, increase of synthesis of IFNalpha and IFNgamma by the cells of Peyer's plaques, the splen and thymus. The obtained results prove the immunological effect of the probiotic preparation Acilact, based on the strains L. acidophilis NK1 and L. acidophilis K3(111)24.

[Characterization of protection mechanisms in patients with drug-resistant pulmonary tuberculosis].

Examining the performance of the local protective system has indicated that patients with drug-resistant pulmonary tuberculosis in the presence of the higher count of cytotoxic lymphocytes had the diminished activation of lymphoid elements of bronchoalveolar lavage (BAL) and decreased alveolar macrophageal production of active oxygen forms. However, there was a drastically increased formation of active oxygen forms in the BAL macrophagues during mycobacterial phagocytosis, which may result to their death. At the same time, the decreased production of gamma-interferon in the BAL cells was found in patients with drug-resistant tuberculosis (8.0 +/- 3.0 U/ml versus 10.7 +/- 2.0 U/ml). In such patients, the generation of alpha-interferon was 105.0 +/- 38.0 U/ml versus 187.0 +/- 72 U/ml in patients with tuberculosis caused by drug-resistant Mycobacterium tuberculosis. In patients with drug-resistant tuberculosis, the lower production of alpha- and gamma-interferons in the BAL cells leads to their decreased regulatory effect on the mechanisms of local defense of the lung. The drastically enhanced production of active oxygen forms, which has been ascertained in patients with drug-resistant tuberculosis, is able to result in the death of macrophages, the release of lysing enzymes into the tissues surrounding the lung; the higher count of T cytotoxic lymphocytes, the lower levels of cells in apoptosis, and mycobacterial resistance to antibacterial drugs deteriorate the course of pulmonary tuberculosis in this category of patients.

[Protective action of leukinferin during radiotherapy of oncologic patients]. / Zashchitnoe deistvie leikinferona pri luchevom lechenii onkologicheskikh bol'nykh.

In clinical observation on 248 patients with breast cancer IIb-III-b stages given radiotherapy on breast gland, parasternal and axillary-subclavian regions (total doses 40 Gr for each) before mastectomy was shown, that use LF im 2-3 times a week through the course of therapy decreases statistically significant pancytopenia, induced by radiation. Quantity leukocytes was even increase in a process of therapy. Frequency of anemia and lyphopenia was decreased almost 3 times. E-RFC were depressed also more slight, then in the group without immunocorrection and after mastectomy practically, restored. IFN-gamma production by T-lymphocytes was not changed and essentially more high then in the comparative group. The presented data are shown, that LF provides a defensive action on hematological indices and immune effectors function in oncological patients during radiotherapy.

[Therapeutic antiradiation properties of leukinferon]. / Protivoluchevye terapevticheskie svoistva leikinferona,

In experiments with three species of animals (mice, rabbits, monkeys) irradiated with sublethal and lethal doses of gamma-irradiation, it was observed, that leukinferon used in 4 hours or 10 days after provided antiradiation therapeutical effect. When lethal dose was used (mice) the survival of animals was significantly increased. The preparation decreased depression of the functional activity of leukocytes as it was observed with IFH-alpha and gamma-production. Pestoring this function was accelerated. Phenomena pancytopenia and thrombocytopenia induced by radiation were decreased. Therapeutical effect was explained with capacity of the preparation to defence the hemopoietic organs from the radiation and to stimulate hematopoiesis. So, spleen weights and quantity of cells into bone marrow were higher in experimental group in comparison with control at any observation. CFUs were also higher (with optimal dose of preparation). Stimulation of the restoring processes was confirmed also by more intensive increasing of the reticulocyte quantities in the circulation of experimental monkeys within 20 days. Then their level became more close in both groups. The preparation stimulated also differentiation of immune effectors: immature neutrophils were absent in the circulation of experimental monkeys. Production of IFN-gamma (which is function of T-lymphocytes) was restored more fast. As a result, immunoreactivity of monkeys in experimental group was more complete and restored faster: the growth of the automicroflora on the skin surface became to increase 7 days later and was restrained. Leukinferon hindered the development of acute radiation sickness symptoms.

[Antiradiation effects of leucynferon on dogs and guinea pigs]. / Protivoluchevaia éffektivnost' leikinferona u sobak i morskikh svinok.

In experiments with two species of animals (dogs, guinea pigs) irradiated with sublethal and lethal doses of gamma-rays, it was observed, that leucynferon had antiradiation effect. Course of injections: dogs--8 injections subcutaneus: 2.0 ml (1, 3, 5, 8, 12, 14, 21, 34 days after irradiation); guinea pigs--14 injections subcutaneus, 0.2 ml (1-14 days after irradiation). Therapeutical effect was explained by capacity of the preparation to defend the hemopoietic organs from the radiation and to stimulate hemopoiesis. Leucynferon hindered the development of acute radiation sickness symptoms. Immunoreactivity of dogs and guinea pigs in experimental group was more complete and restored faster. The growth of the automicroflora on the skin was restrained. Production of interferon-gamma (which is a function of T-lymphocytes) was restored faster.

[Pharmacokinetics of interferon administered rectally]. / Farmakokinetika interferona pri rektal'nom vvedenii.

Human leukocyte and recombinant interferon administered rectally to rabbits in a dose of 10,000 units per kilo body weight was found in the blood serum within 30 min. A certain level of interferon persisted for 5 hours after which time it disappeared from the serum. Recombinant interferon was eliminated more rapidly than leukocyte interferon. Repeated administrations of interferon at 5-hour intervals increased the time of its presence in the serum. The rectal method of interferon administration was used clinically in infants under one year. Its pharmacokinetics did not differ from that after administration by other routes.

[The humoral immunity system of mice with experimental slow influenzal infection]. / Sostoianie sistemy gumoral'nogo immuniteta u myshei pri éksperimental'noi medlennoi grippoznoi infektsii.

The status of the interferon system and level of immunoglobulins were studied in C57BL6 mice with slow influenza infection. These mice showed signs of immunosuppression: low endogenous interferon production, synthesis of alpha- and gamma-interferon by splenocytes of these mice in vitro 4-8 times lower than by those of the controls, lower levels of IgG in the blood serum. These data indicate general suppression of humoral immunity.

[Experimental myocardiopathy caused by the herpesvirus]. / Eksperimental'naia miokardiopatiia, vyzvannaia virusom gerpesa.

Mice weighing 18--20 g were inoculated with herpes simplex virus type I. The rate of pathological changes in the myocardium was found to depend on the route of virus inoculation and the time of heart examinations in the infected animals. The development of myocardiopathies was not determined by the virus dose used in the test. An immunosuppressant drug, imurane, reduced the rate of heart affections. Pathomorphological changes in the heart were of parenchymatous-interstitial nature, with the leading role of lesions of myocardium muscle cells proper and secondary development of microcirculation disorders. The rate of heart lesions increased when herpes and influenza viruses were given to mice simultaneously; staphylococcus toxin had the same effect.

[Leukocyte interferon reaction in patients with primary immunodeficiencies]. / Interferonovaia reaktsiia leikotsitov u bol'nykh s pervichnymi immunodefitsitami.

The capacity of leukocytes from children with primary immunodeficiency to produce alpha- and gamma-interferons in vitro was studied. Interferon response of leukocytes in most of the patients examined was found to be practically unchanged. The immunostimulating therapy in some cases exerted a regulating effect on leukocyte capacity for interferon production. It is assumed that the interferon-producing function of T lymphocytes may be preserved in patients suffering from primary immunodeficiency.

[Expression of receptors for human alpha- and gamma-interferons on the surface of peripheral blood mononuclear cells in viral infections]. / Ekspressiia retseptorov dlia chelovecheskikh alpha- i gamma-interferonov na poverkhnosti mononuklearnykh kletok perifericheskoi krovi pri virusnykh infektsiiakh.

Expression of receptors on peripheral blood mononuclears of donors and patients with viral infections during therapy was studied using FITC-labeled monoclonal antiidiotypical antibodies with the "internal image" of human alpha- and gamma-interferons and monoclonal antibodies to these interferons. Activation of the immune system caused by infection modifies the expression of interferon receptors and leads to appearance of membrane-bound interferons, mainly gamma-interferon.

[The interferon reaction of the leukocytes and the natural killer activity in patients with acute viral hepatitis B undergoing interferon treatment]. / Interferonovaia reaktsiia leikotsitov i aktivnost' estestvennykh killerov u bol'nykh ostrym virusnym gepatitom B pri lechenii interferonom.

The interferon response of leukocytes (IRL) alpha and gamma as well as the functional activity of natural killers (NK) were studied in patients with the verified diagnosis of acute viral hepatitis B (AVH-B) treated with leukinferon (a preparation of natural interferon-alpha and cytokines) and reaferon (recombinant alpha 2 interferon). The effect of therapy with LF and RF in patients with AVH-B manifested by an increase in the functional activity of NK up to complete normalization after termination of the course of therapy. In the group of patients treated with LF as a result of therapy IRL-alpha increased by the end of the treatment and in the convalescence period. The observed activation of NK and the IF-alpha system under the effect of IF preparations in patients with AVH-B correlated with enhanced elimination of HBsAg.

[Tumor necrosis factor in medicinal interferon preparations]. / Faktor nekroza opukholi v meditsinskikh preparatakh interferona.

In response to virus induction a culture of donor leukocytes alongside with interferon (IF-alpha) produced a factor of tumor necrosis (TNF). The kinetics of TNF and IF-alpha biosynthesis did not depend on the kind of IF used for priming, was rapid, with maximum production within 7-8 hours. Antibodies to IF-alpha and IF-alpha had no effect on TNF production, while antibody to TNF did not reduce IF-alpha yields. TNF in detectable titres was present in medical preparations of native IF-alpha but was absent in preparations of recombinant IF-alpha and IF-alpha as well as in an injection preparation of IF purified by chemical methods.

[The use of a complex preparation of alpha-interferon and first-phase immune-response cytokines--leukinferon]. / Primenenie kompleksnogo preparata al'fa-interferona i tsitokinov pervoi fazy immunnogo otveta--leikinferona.

Cases of successful treatment of severe neurological complications, developing as a consequence of diphtheria intoxication, by injections of leukinferon, a new combined preparation of alpha-interferon and other cytokines of the first stage of immune response, are described. Toxico-allergic polyneuropathy with sensory, reflex, motor (tetraparesis) disturbances and the bulbar syndrome developed in males after nasopharyngeal diphtheria. For the first time effective and rapid therapy of the bulbar syndrome and other disturbances, developing in connection with the demyelinating toxico-allergic process, was shown to be possible due to the use of leukinferon in combination with other therapeutic measures. The preparation proved to be highly effective in the treatment given with a view to arrest the development of intercurrent infectious complications in severely ill, bedridden patients receiving prednisolone. Leukinferon produces a pronounced effect even in patients receiving massive doses of corticosteroids, thus making it possible to shortly abolish the use of these preparations.

[The clinical efficacy in using leukinferon in adults with diseases caused by the varicella-zoster virus]. / Klinicheskaia éffektivnost' primeneniia leiinferona u vzroslykh pri zabolevaniiakh, vyzvannykh virusom vetrianoi ospy.

To achieve more effective treatment of varicella (chickenpox) and herpes zoster in adults, a wide-spectrum immunocorrective agent containing, together with alpha-interferon, a number of other cytokines of the first phase of immune response was used. In patients with the different severity of disease leukinferon induced a rapid decrease in the severity of the disease, arrested the development of new elements on the skin and the buccal mucosa, and reduced the duration of the fever period. When used in such forms as intramuscular injections in combination with the irrigation of the buccal mucosa and ointment, leukinferon proved to be a highly effective preparation for the treatment of diseases caused by varicella-zoster virus.

[The combined therapy of patients with gonorrheal-chlamydial urogenital infections by leukinferon immunocorrection]. / Kompleksnaia terapiia bol'nykh s gonoreino-khlamidiinoi urogenital'noi infektsiei s immunokorrektsiei leikinferonom.

The adjuvant injection of wide-spectrum immunocorrector leukinferon to 45 males with gonorrheal-chlamydial urogenital infection receiving tarivid and doxicicline made the treatment shorter and the number of inflammatory complications and recurrences less numerous. Leukocyte and lymphocyte counts returned to normal values 6 days earlier and so did immunological indices. In control subjects (20 patients) on immunocorrection with tactivin inflammation persisted longer, urogenital complications were not cured, chlamydial recurrences occurred in 10% of the patients, immunological normalization was not reached.

[Leukinferon in immunological correction of acute inflammatory diseases of the abdominal organs]. / Immunokorrektsiia leikinferonom pri ostrykh vospalitel'nykh zabolevaniiakh organov briushnoi polosti.

Addition of (intramuscular+intravenous) leukinferon (LF) to the schemes for the treatment of acute peritonitis promoted a more rapid positive development of the time course of clinical signs and decreasing of leukocytosis in the presence of a pronounced tendency to normalization of the main immunological indices i. e. the counts of differential T-lymphocytes and T-helper cells. There was also activation of neutrophil phagocytic function. A rapid decrease in objective signs of endotoxicosis was recorded: the intoxication leukocytic index and the level of medium-mass molecules. In parallel with the decrease in the intoxication leukocytic index, there was a decrease in cytosis of the peritoneal exudate. The use of LF in the treatment of elderly patients with acute cholecystitis eliminated the clinical signs and normalized the main laboratory indices without surgical interventions which allowed one to make a planned operation with the minimum risk.

[Leukinferon in the treatment of patients with acute viral hepatitis b]. / Primenenie leikinferona v lechenii bolnykh ostrym virusnym gepatitom B.

Leukinferon activity was studied in a controlled trial including 30 patients with acute viral hepatitis. The disease ran a moderate severity course in the majority of the patients. Leukinferon, a combined preparation of natural interferon and cytokines produced by virus-induced leukocytes, has marked immunomodulating properties at moderate antiviral activity. Leukinferon was administered intramuscularly for 10 days according to the following scheme: day 1-1 sample 3 times, day 2-1 ampule 2 times, day 3-10-1 ampule a day (overall 1 x 10(5) U of interferon). Due to leukinferon the symptoms of intoxication declined, hepatic biochemistry normalized more rapidly as well as the period of viremia and antigenemia. Positive clinical trends correlated with interferon system improvement and activation of natural killers. 6 months later complete recovery was registered in all leukinferon-treated subjects.

[Leukinferon in combined therapy for acute pulmonary tuberculosis]. / Leikinferon v kompleksnoi terapii ostroprogressiruiushchego tuberkuleza legkikh.

Experiments on 140 CBA and C57BL/6 mice and studies of 163 patients with acute pulmonary tuberculosis have indicated that leukinferon has a immunomodulating effect on morphological reactions in the lung and on the clinical course of the disease. They have shown that leukinferon plays an important role in the activation of exudate macrophages and in the acceleration of their differentiation in experimental tuberculosis and that there is a rapid elimination of Mycobacterium tuberculosis from the involved organs without production of the L-forms of the causative agent when immunomodulation is used. At months 2-3, the patients with acute pulmonary tuberculosis showed the accelerated processes of detoxification, abacillation, infiltrate resolution, and decay cavity closure during hemo- and immunomodulation with the normalized production of cytokines (gamma-interferon and tumor necrosis factor-alpha). During 6-month therapy, a severe pulmonary process was arrested in 84% of cases and some patients were operated on (76% in the comparison group). The morphological effect of leukinferon was to increase mononuclear infiltration and to normalize a lung connective tissue response, by further decreasing the rate of inflammation.