Russian journal of immunology : RJI : official journal of Russian Society of Immunology最新文献

We have studied the changes in the serum level of the following cytokines during the course of treatment of nosocomial pneumonia (NP): pro-inflammatory--IL-1alpha and IL-6, chemoattractive--IL-8, anti-inflammatory--IL-4 and IL-10, and differentiating-activating--IFN-gamma and TNF-alpha. It has been found that at the time of admission of the patients the clinical severity of their condition was correlated with increased levels of all circulating cytokines except for IFN-gamma, the level of which was low. An adequate ethiotropic therapy helped to clear the clinical symptoms of infection and intoxication in 1-2 weeks. The level of circulating pro- and anti-inflammatory cytokines, IL-8, and TNF-alpha was decreasing, however, the level of IFN-gamma did not change significantly during 15 days. The ratio IFN-gamma/IL-10 did not change much but was slightly low during the treatment of the severe form of NP. Radical positive changes in the cytokine dynamics were achieved after the addition of leukinferon to the ethiotropic therapy.

When human sera samples are tested for anti-hepatitis C virus (HCV) antibodies using different ELISA kits as well as immunoblot assay kits discrepant results often occur. As a result the diagnostics of HCV infection in such sera remains unclear. The purpose of this investigation is to define the limits of HCV serodiagnostics. Overall 7 different test kits of domestic and foreign manufacturers were used for the sampled sera testing. Preliminary comparative study, using seroconversion panels PHV905, PHV907, PHV908 was performed and reference kit was chosen (Murex anti-HCV version 4) as the most sensitive kit on the base of this study results. Overall 1640 sera samples have been screened using different anti-HCV ELISA kits and 667 of them gave discrepant results in at least two kits. These sera were then tested using three anti-HCV ELISA kits (first set of 377 samples) or four anti-HCV ELISA kits (second set of 290 samples) at the conditions of reference laboratory. In the first set 17.2% samples remained discrepant and in the second set - 13.4%. "Discrepant" sera were further tested in RIBA 3.0 and INNO-LIA immunoblot confirmatory assays, but approximately 5-7% of them remained undetermined after all the tests. For the samples with signal-to-cutoff ratio higher than 3.0 high rate of result consistency by reference, ELISA routing and INNO-LIA immunoblot assay was observed. On the other hand the results of tests 27 "problematic" sera in RIBA 3.0 and INNO-LIA were consistent only in 55.5% cases. Analysis of the antigen spectrum reactive with antibodies in "problematic" sera, demonstrated predominance of Core, NS3 and NS4 antigens for sera, positive in RIBA 3.0 and Core and NS3 antigens for sera, positive in INNO-LIA. To overcome the problem of undetermined sera, methods based on other principles, as well as alternative criteria of HCV infection diagnostics are discussed.

The goal of the current work is to determine the role of the TNF-alpha on the activation of the bacterial growth in an in vivo system. In order to reach this goal we studied the dynamics of the reproduction of vegetative forms of Salmonella and the recultivation of non-cultivating forms of Salmonella in infected animals. Experiments have been conducted both on animals that had been injected with exogenous TNF together with bacterial suspension and on animals that had been exposed to gamma-radiation before infection, since it is known that irradiation increases the secretion of TNF. We demonstrate that in all cases the increase in the level of TNF-alpha in animals leads to the activation of the Salmonella growth. Moreover, in this paper we present the data obtained by the method of molecular display on the identification of genes that are highly expressed in the Salmonella cells cultivated in vitro in the presence of TNF.

Integral parameters of NK cell cytotoxicity and IFN production measured as square of the area under the cytotoxic and IFN titer curves were correlated with each other. The NK and IFN parameters were also calculated by the standard method using effector : target cell (ET) ratio and correlated with each other again. It was shown that NK cell cytotoxicity and IFN production by normal human PBL reacting against K562 targets correlated positively. At the same time, individual variations of the correlation coefficients obtained by the standard ET technique enabled us to divide all the tested subjects into subgroups with higher and lower positive correlation of the NK and IFN parameters. These subgroups showed differences in standard parameters and their correlation coefficients obtained at ET ratios 100:1 and 6:1; integral parameters of NK cell cytotoxicity and IFN production, as well as their correlation. The data obtained confirm that natural cytotoxic reactions mediated by normal human PBL provide an efficient intimate mechanism for splitting biological signals generated in response to target cells.

Cytokine mRNA expression was studied in human long-term cell cultures of different origin: J-96 and J-41 (monocytic leukemia), SW-13 (paradrenal adenocarcinoma), and MT-4 (T-cell leukemia), in response to IFN-alpha and IFN inducers (kagocel and cycloferon). Cytokine mRNA level in the cell cultures was measured by the RT-PCR method using 11 primer pairs for the following cytokines: IFN-alpha, IFN-gamma, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18 and TNF-alpha. It was shown that IFN-alpha and IFN inducers possess an ability to regulate different cytokine mRNAs. Treatment of the cells with IFN-alpha resulted in expression of mRNAs for IL-2, IL-4, and IL-8. Kagocel induced production of IFN-alpha, IFN-gamma, and IL-2 mRNAs, and cycloferon--IFN-gamma, IL-2, IL-4, and IL-8 mRNAs. It is suggested that antiviral effects of these inducers, in general, can be attributed to imitation of cytokine responses observed in viral infection and, as a result, can lead to starting-up of cellular defense antiviral mechanisms even before action of viruses. Conclusion is made that IFN and IFN inducers may act as regulators of cytokine activity.

Polyprenols are an integral part of all living cells including prokaryotic and eukaryotic ones. These compounds take part in biosynthesis of glycoproteins. We have found that phosphates of polyprenols may act as effective antiviral agents with a wide spectrum of activity. One of such antiviral agents received from Pinus sativum polyprenols was named phosprenyl. Earlier we showed that phosprenyl expressed direct antiviral effect, while having mild immunomodulatory activity. In the present study we further evaluated influence of phosprenyl on the immune system. The drug was found to inhibit an early phase of IL-1 and Con A interaction in spleen cells as well as lypoxigenase activity and expression of IL-2 receptors. At the same time, phosprenyl induced NK cell activity and early TNF-alpha production. Basing on all these data we proposed that polyprenols could be considered as a "label" which grants a possibility to the innate immune system to recognize infection at the early stages and govern the acquired immunity.

Interferon homeostasis was studied in children with bronchial asthma (BA) at different stages of the disease. The control group consisted of 10 children with no predisposition to atopic reaction. Children with BA showed a disfunction of interferon homeostasis, with a significant decline in the leukocyte ability to produce IFN-alpha and IFN-gamma. The concentration of blood serum IFN-gamma was reduced at all stages of BA, with a more significant decrease during BA attacks than during the remission period. IFN-gamma synthesis disturbances in BA children were stable and resistant to therapeutic treatment by recombinant IFN-alpha2b (Viferon). Viferon normalized the production of IFN-alpha, and the effect remained unchanged during a half-year examination period. Thus, Viferon appears promising as part of a complex therapy for children with BA at remission stages and frequent respiratory infections.

The present work is dedicated to the investigation and complete characterization of the interferon (IFN) and cytokine profile in 8 patients with genital herpes caused by the herpes simplex virus type 2 (HSV-2). The control group included 42 healthy individuals. The patients with genital herpes showed a significant reduction in the ability to produce IFN-alpha and a slight decrease in the ability to produce IFN-gamma. At the same time, most of the patients had high titers of circulating plasma IFN and of IFN that is spontaneously produced by blood cells, which is suggesting the presence of the active acute stage of the disease. The immune reaction in patients with HSV-2 infection has been characterized based on the analysis of the stimulation and suppression of mRNA expression for cytokines. Activation of the cellular and humoral immunity as well as abnormalities in B-cell immunity was observed in most cases of acute genital herpes.

The polyethiology of the respiratory diseases and the lack of effective vaccines to prevent them (except for influenza) underline the need for clinical trials and the practical application of immunomodulatory preparations that could become part of the group of anti-viral drugs with a wide range of activity. It has been demonstrated that amixin and poludan, the drugs made in our country, cause an increase of the serum IFN level, enhance the ability of leukocytes and lymphocytes to produce IFN-alpha and IFN-gamma, and lead to the activation of NK and peripheral blood phagocytes. In other words, they have an immunostimulating activity. The number of CD3(+), CD4(+), CD8(+), CD19(+) cells, the level of the Ig A, IgG, IgM and several other parameters of the immune system were not affected by these drugs. It has been demonstrated that amixin and poludan show good drug tolerance, without side effects on the hemogram in individuals who were taking these drugs just for disease prevention. The studied immunomodulators have a significant prophylactic activity in the cases of the polyethiologic group of acute respiratory viral infection during the seasonal peak of the disease, with a coefficient of efficiency of 3.6 (amixin) and 2.1 (poludan), and corresponding protection indices of 72.1% and 52.7%. Having the same chance of getting infected, individuals protected with these drugs often have the disease in a milder or asymptomatic form.