[Anticytokine therapy of allergic asthma].

Bronchial asthma is a chronic inflammatory disease of the airways that is characterized by episodes of shortness of breath, expiratory dyspnea, cough, wheezing, and pulmonary emphysema. At the present time, asthma is a global public health problem and affects about 5% of the worldwide population. Although a wide range of anti-inflammatory drugs is available, uncontrolled or poorly controlled asthma is still a problem, requiring the development of novel therapeutic approaches. Intense studies of the molecular mechanisms of asthma in transgenic animals performed since the 1990s implicated cytokines, such as IL-4, IL-5, and IL-13, and their receptors in the initiation and maintenance of asthma. These findings led to anticytokine therapy as a novel approach for bronchial asthma treatment. To date, many preclinical and clinical studies have been performed in this field especially with drugs based on humanized monoclonal antibodies, soluble receptors, peptide inhibitors, etc. The review summarizes the data from preclinical and clinical studies of anti-cytokine therapeutics in humans.

RNA INTERFERENCE: NEW APPROACH TO THE TREATMENT OF ALLERGIC ASTHMA (A REVIEW).

Asthma is among the most common chronic disorders of airways, which affects both children and adults. Asthma being a common disease among different segments of population, it has a high mortality rate and, in the absence of appropriate care, affects the quality of life and leads to economics losses. In a view of continuing growth in the incidence of asthma, it is important to find relevant biological targets for developing new approaches to astma therapy. Recent advances in molecular immunology, genetics, and bioinformatics allowed genes involved in the pathogenesis of asthma to be identified, which provided prerequisites for the development of new types of drugs that can regulate the activity of pathogenically significant genes. To date, a number of technologies for sequence-specific gene regulation (ASO, ribozymes, DNAzymes, EGS, DNA-decoys, U 1-adapters) are available, but RNA interference is the most promising approach in both terms of efficacy and financial cost. This review focuses on the generalization and analysis of experimental data regarding the use of RNA interference technology for the treatment of astma.

[Histamine releasing and immunomodulating activity of dental restorative materials].

Histamine releasing and immunomodulating activity of the following dental restorative materials (DRM) - Prizmafil, Filtek Z250, XRV Herculite Prodigy, Glasiosite, Te-Econol, Valux Plus, Polofil Supra were studied. It was shown that DRM under study as a rule did not possess the ability to release histamine (H) from human blood basophile (BB) excluding Filtek Z250 which release H from BB in patients with allergy and sound donors. The studied DRM implanted under mouse skin were able to modulate immune response to the allergen, at that some of them increased antibodies of IgE-class forming and other suppressed immune response caused by IgG-antibody forming. Received data have certain significance in the scheme of safety evaluation and individual assessment of DRM having acceptable biocompatibility for specific patient.

[Histamine releasing activity of dental materials as the indicator of their biocompatibility].

Different types of dental materials (DM) were studied for their capacity to release histamine in vitro from basophils of whole blood of allergic patients and healthy donors using automated and computerized glass fiber-based leukocyte histamine release test (LHRT). It was shown that some types of DM possessed ability to release histamine from basophils and some didn't. There were no differences in histamine releaseability from basophils obtained from allergic patients and healthy donors. LHRT gives opportunity to recognize of DM possessing high or low histamine releaseability as well as to detect individual sensitivity to different DM. Thus, LHRT can be used for preliminary assessment of DM for their biocompatibility and also for individual selection of suitable DM for particular patient to avoid unwanted side effects.

[Immunomodulating activity of dental materials used for filling of dental root canals].

In experiments on mice immunomodulating activity of root canal pastes (Septodent, Foredent and Sealite Regular) was studied concerning immune response to model allergen. In order to study immunomodulating effect of root canal pastes the authors have used the model of standardized immunization by model allergen ovalbumin (OA) of mice (CBA x C57BL/6)F1. OA (Sigma) was used as model allergen in all experiments both for mice immunization and for testing anti-OA IgE- and IgG-antibodies in reaction of passive skin anaphylaxis in rats and in reaction ELISA. It was established that the tested pastes led to changes in antibody formation dynamics of the IgE- and IgG-classes, at that some of them produced immunosuppression. In that way root pastes could weaken immune protection increasing risk of different diseases rise.

[Histamine-releasing activity of dental materials employed as root canal filling].

Four samples of dental materials (DM) estd for root canal filling, Septodent (S), Zinkoxide (Z), Foredent (F) and Cialite Regular (CR), were studied for their ability in vitro to release histamine (HR) employing the computerized fiber glass based histamine release assay using whole blood from allergic patients and healthy donors. It was found that F induced high and S low levels of HR from blood basophils from both allergic and non-allergic subjects. Z and CR did not induce HR from blood basophils similar to the negative control. The HR assay may be a useful method for preliminary investigation of DM employed for root canal fillings for safety as well as for selection of specific DM for individual patients.

[The effect of structural-chemical characteristics of water-soluble polyelectrolyte complexes of ovalbumin on their immunological properties]. / O vliianii strukturno-khimicheskikh osobennostei vodorastvorimykh poliélektrolitnykh kompleksov oval'bumina na ikh immunologicheskie svoistva.

Immunogenicity of soluble protein antigens in the complexes with synthetic polyions may be regarded as depending both on the nature of polymer carrier and the structure of the protein-polyelectrolyte complex. The immunogenicity of stable soluble complexes of ovalbumin (OA) with polycation - quaternized poly-4-vinylpyridine (C-1) and copolymer of acrylic acid and 2-methyl-5-vinylpyridine (C-2) have been evaluated. Immunization of mice by C-1 have induced a vigorous formation of the anti-OA IgG antibodies and IgE homocytotropic antibodies, while immunogenicity of OA in C-2 was comparable with that of OA alone. The analysis of the structural-chemical features of the complexes investigated has shown that enhanced immunogenicity of C-1 may be due to (1) the non-homogeneous distribution of protein globulae among polycation macromolecules and to (2) the formation of complex with an asymmetrical structure, to (3) the high ability of C-1 to adsorb on a surface of the lymphoid cells and to induce a formation of intercellular aggregates. An enhancing of a stability and a size of C-2 in the presence of Cu2+ shows no influence on a immunogenicity of OA. An immunogenicity of both types of complexes does not depend upon the access of determinants of OA to antibodies so far as it has been shown that complex formation in both cases are not accompanied by an alteration of antigenicity and allergenicity of OA.

[Histamine-releasing activity of acrylic plastic materials]. / Gistaminvysvobozhdaiushchaia aktivnost' akrilovykh plastmass.

The histamine-releasing activity of acrylic plastics (ftorax, stomacryl, ethacryl) used for denture making and maxillofacial prostheses was studied by automated and computer-aided fiber glass method for evaluating histamine release from whole blood basophils. The results indicate that some plastics made by the thermo-polymerization method (for example, ethacryl) are characterized by higher histamine-releasing activity than the plastics made by polymerization using superhigh frequency electromagnetic energy. The method is recommended for preliminary screening of new polymers intended for dentistry and for individual selection of materials with consideration for their safety and strength characteristics.

[Chemical modification of allergen leading to changes in its epitopic activity]. / Khimicheskaia modifikatsiia allergena, vedushchaia k izmeneniiu ego épitopnoi aktivnosti.

Modification of a model allergen ovalbumin (OA) with succinylation led to a decrease of its allergenicity measured by passive cutaneous anaphylaxis reaction, RAST inhibition assay and basophil histamine release. Modified OA stimulated OA-specific T-cell hybrid 3DO-548 to produce IL-2 at the same level as in case of non-modified OA. Modified OA did not induce anti-OA IgE, but did induce anti-OA IgG antibodies. This approach to chemical modification of allergen-selective blockade of B-cell epitopes while not affecting T-cell epitopes suggests new opportunities in creation of safe and effective allergovaccines.

[Role of allergic responses of peripheral blood leukocytes in the pathogenesis of experimental allergic (pertussis) encephalomyelitis]. / O roli allergicheskikh reaktsii leikotsitov perifericheskoi krovi v patogeneze éksperimental'nogo allergicheskogo (kokliushnogo) éntsefalomielita

Stable leukocytosis and lymphocytosis were observed in the peripheral blood of guinea pigs from the 14th day after their sensitization with B. pertussis oil suspension. A shift to the left occurred in the leukocytic count. After the contact of leukocytes with the specific cerebral antigen both in vivo and in vitro leukolysis and allergic alteration of leukocytes which occurred at the last stages of sensitization i.e. at the period of clinical manifestation of the experimental allergic encephalomyelitis (EAE) involved mainly the granulocytes. These phenomena are supposed to be caused by the anticerebral antibodies which appear in the blood at this stage of EAE, i.e. in the mechanism of development of EAE allergic reactions of the immediate type in combination with allergic reactions of the delayed type.

Effect of misoprostol on the secretion of histamine from basophils of whole blood.

BACKGROUND: Misoprostol (MSP), the synthetic prostaglandin E1 (PGE1) analog, possesses multifunctional features, including modulating some inflammatory aspects of immune and allergic disorders. OBJECTIVES: To investigate the effect of MSP on histamine release (HR) from basophils of whole blood using anti-IgE, specific allergens, and calcium ionophore. METHODS: The study was performed using the automated glass fiber-based whole blood leukocyte histamine release test (LHRT). RESULTS: Very low concentrations of MSP produced a marked inhibition of HR induced with anti-IgE. Maximum inhibition was observed at 10-9 M. It was also shown that the levels of HR inhibition with MSP varied at different incubation times. The greatest inhibition of HR was noted at 1 to 2 hours of incubation at MSP concentrations of 10-8 and 10-9 M, respectively. Incubation of blood from allergic patients at the optimal MSP concentration and optimal elapsed time (2 hours) resulted in significant reductions of allergen-specific HR induced by both Timothy pollen grass allergen and D.pteronissinus. Incubation of blood with varying concentrations of MSP and subsequent stimulation with calcium ionophore A23187 also inhibited HR from basophils. In the latter case, the most effective concentrations of MSP ranged from 10-8 to 10-6 M. CONCLUSIONS: This study demonstrated that MSP can inhibit basophil HR indicating a potentially beneficial role of PGE1 analogs as pharmacotherapy for allergic diseases.

Modified allergen immunotherapy: effect on immunoglobulin E production.

New forms of allergen immunotherapy are proposed employing modified allergens that induce T-cell responses without associated increased IgE-related responses. Synthetic polyelectrolytes attached to an analyte amy modulate T- and B-cell function, producing effective desensitization and altering immunoglobulin production dependent on the physico-chemical nature of the carrier molecule.

[Specifically reactive cells in experimental allergic pertussis encephalomyelitis]. / Spetsificheski reaktivnye kletki pri éksperimental'nom allergicheskom kokliushnom éntsefalomielite.

Dynamics of emergence of specific reactive cell (SRC) with respect to the brain antigen in the draining regional lymph nodes and peripheral blood was studied in experimental whooping cough allergic encephalomyelitis (EAE) in guinea pigs. The greatest number of SRC in the regional lymph nodes, that markedly decreased by the 9th day of sensitization, was revealed in the middle of the EAE incubation period (the 6-7th day), whereas the peripheral blood showed the highest SRC number during this period. The SRC number rose in the regional lymph nodes and dropped in the peripheral blood at the height of EAE progress (the 20th day). It is concluded that SRC found may be attributed to T lymphocyte population.

Latex aeroallergen quantification in hospitals of Moscow, Russia.

BACKGROUND: Health care workers (HCWs) who use latex gloves regularly are at a significant risk for developing allergic sensitization to natural rubber latex (NRL) proteins. The airborne route of exposure presents a hazard for sensitization and subsequent allergic symptoms. OBJECTIVE: The purpose of this study was to measure the content of the NRL proteins in the air of work areas (laboratories, treatment rooms, operating rooms, examination rooms, and dentist's treatment rooms) in eight Moscow hospitals where the employees used powdered latex gloves. METHODS: The air samples were collected by a volumetric filtration method using a static air sampler at a flow rate of 3 L/second. Airborne particles were collected onto polytetrafluoroethylene filters rated 99.9% efficient at 0.3 microm. The NRL allergens were extracted from the air filter samples in phosphate-buffered saline and quantified by an inhibition immunoassay using a five-person pool of sera containing latex-specific human immunoglobulin E. RESULTS: The airborne latex allergen concentrations in 11 areas (including positive control) where latex gloves were used varied from 5 to 26 ng/m3. Conversely, in 12 areas where latex gloves were seldom used or where powdered-free latex gloves were used allergen levels were not detectable (including two negative controls). The highest concentration of latex allergen (26 ng/m3) was found in an examination room of a gynecology department. Low and moderate concentrations were detected in most operating rooms, and low concentrations in the laboratories and treatment rooms. CONCLUSIONS: This study indicates that, in general, the airborne NRL concentrations in the work areas of Moscow hospitals are rather low compared with NRL concentrations reported from American hospitals and are dependent on the intensity of latex glove usage.

In vivo and in vitro immunomodulation induced by the extract of the mycelium fungus Polyporus squamosus.

The mycelial mass of the fungus Polyporus Squamosus strain 64 (PS-64) was disintegrated by mechanical and ultrasound treatments. After centrifugation, the supernatant containing the disintegrate was dialyzed and lyophilized. The resultant PS-64 extract was subsequently investigated as an immunomodulator of IgE and IgG responses to ovalbumin (OA) in (CBAxC57BL/6)F1 mice using passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA), respectively. Multiple injections of PS-64 extract in doses of 1.5, 15, and 150 mg/kg administered before the primary or secondary immunization of mice with OA resulted in a dose-dependent inhibition of both IgE and IgG antibody responses to OA. In contrast to the inhibition of the anti-OA IgE response noted during the entire 3-week observation period, the anti-OA IgG response was restored to control level by the third week of secondary immunization. The glass microfiber-based whole blood histamine release assay demonstrated that various concentrations of the PS-64 extract did not influence histamine release induced either by anti-IgE or by specific allergens from basophils derived from whole blood of allergen-sensitized patients. Using the hemolytic plaque assay, significant suppression of IgM-secreting cell formation was noted in (CBAxC57BL/6)F1 mice administered various doses of the PS-64 extract before immunization. The PS-64 extract inhibited the in vitro proliferation of human mononuclear cells upon stimulation with phytohemagglutinin (PHA). In a dose-dependent manner, the PS-64 extract also inhibited delayed-type hypersensitivity reaction and skin graft rejection, similar to the effect noted with usage of Cyclosporin A (CsA) in (CBAxC57BL/6)F1 mice. Our investigation suggests that the immunomodulatory effects of PS-64 should be studied further for potential clinical therapeutic utility.