[Evolutionary admonition: allergy].

The paper concerns phylogeny development of allergic reactivity, the most probable antecedents of allergic IgE antibodies, high affinity IgE receptor (Fc(epsilon)RI), presents comparative character of IgE - Fc(epsilon)RI and IgY- CHIR-AB1 interactions. The paper has given an insight of allergy as evolutionary selected reactivity for highly organized animals. This reactivity is directed to organization of allergen-specific inflammation and serves as biologically expedient, high-specific and high-sensitive reaction in response to allergen entering into the organism because of barrier tissue dysfunction. Such insight has raised a question on consequences of thoroughgoing allergy reactivity elimination for highly organized animals and their posterity.

[Molecular basis of allergy control].

The article describes the picture of the interaction between IgE and its high-affinity receptor (Fc(epsilon)RI) leading to cellular triggering and clinical manifestations of IgE-dependent allergy. New understanding of the key event of an allergic response has enabled new pharmacological interventions at this stage.

[Comparative antihistamine and anti-allergic effects of various antihistamine preparations]. / Sravnitel'noe izuchenie antigistaminnoi i antiallergicheskoi aktivnosti nekotorykh protivogistaminnykh preparatov.

AIM: To compare antihistaminic and antiallergic activity of antihistaminic drugs of the latest generation (ebastin, cetirisine, fexofenadine, loratadine) and antihistaminic drugs of the first generation (clemastin) in the same patients with pollenosis. MATERIAL AND METHODS: Skin prick-titration with 10-dilution histamine and specific allergen, provocative nasal titration with 2-dilution histamine and allergen before and after a single intake of H1-antagonists were made in 30 patients in stable clinical remission of pollenosis during maximal antihistamine activity of the above drugs. RESULTS: Systemic administration of the known H1-antagonists suppresses histamine sensitivity of both skin and nasal mucosa in the same degree. Drugs with more potent antihistaminic activity (fexofenadin and cetirisin) inhibited allergen-induced reactions more effectively. The order of the tested drugs by suppression of allergen-provoked skin and nasal reactions (by lowering antiallergic activity) is the following: fexofenadin and cetirisin > ebastin and loratadin > clemastin. CONCLUSION: The above drugs of the latest generation seem to posses antiallergic activity not only due to antihistaminic effect but also due to other mechanisms. Different suppressive action of H1-antagonists reflects also individual sensitivity to different drugs. The factor of individual sensitivity of the patients to a pharmacological action of the drug may be crucial in the selection of the most effective medicine for each patient. This is confirmed by the data of individual sensitivity of the patient to antihistaminic and antiallergic action of H1-antagonists. The illustrated method may be helpful for individual selection of H1-antagonists for treatment of patients with allergic diseases.

[Therapeutic effectiveness of histaglobin preparations in patients with allergic rhinitis and chronic urticaria]. / Terapevticheskaia éffektivnost' preparatov gistaglobina u bol'nykh allergicheskim rinitom i khronicheskoi krapivnitsei.

AIM: To evaluate therapeutic effects of histaglobin drugs (histaglobin and histaglobin-triplex) in patients with continuous allergic rhinitis (CAR) and chronic recurrent (idiopathic) urticaria (CRU). MATERIALS AND METHODS: The drugs were given to 45 patients with CAR and high sensitivity to household allergens confirmed by cutaneous diagnostic tests or high IgE level, and 40 patients with CRU with typical cutaneous lesions. The drugs were injected subcutaneously (a total of 6 injections, 2 ml of solution each) with the interval 2-3 or 3-4 days. Histaglobin was given as 12 mg of normal human immunoglobulin + 0.00015 mg of histamine dihydrochloride. Histamine-triplex as 36 mg of immunoglobulin + 0.00045 mg of histamine dihydrochloride. The treatment was repeated in a months (3 injections). Clinical response was assessed in scores by the scale of clinical symptoms. RESULTS: Histaglobin relieved symptoms of CAR (from 7.34 +/- 0.095 to 1.7 +/- 0.04 scores on the treatment day 28, p < 0.01). After the repeated course CAR symptoms attenuated to 1.6 +/- 0.057 scores). Extranasal symptoms significantly reduced too. Excellent and good results were achieved in 80% of the patients. Positive results were also obtained in 82.5% of CRU patients. Tolerance of histaglobin and histaglobin-triplex was good. CONCLUSION: In the tested regimen, both histaglobin and histaglobin-triplex proved effective in CAR and CRU when routine treatment failed.

[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.

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.

Modulation of Basophil Histamine Release and T Cell Reactivity by Chemically Modified Allergen.

Modification of a model allergen ovalbumin (OA) with succinylation (Suc-OA) led to inhibition of allergen histamine releasing activity as it was tested on basophils of OA-sensitive patients. A whole blood leukocyte histamine release was performed by glass fibre based histamine assay. IgE-binding activity of Suc-OA was significantly reduced as it was shown by RAST inhibition technique. Suc-OA stimulated OA-specific T cell hybrid 3DO-548 and ACP:LK35 to produce cytokine release at the same level as in the case of non-modified OA. Succinylation of OA was concluded to result in selective blockade of B cell and preservation of T cell epitopes of the allergen suggesting a new approach for allergen specific immunotherapy.

Control of Allergen-Induced Histamine Secretion by Human Basophils with F(ab) of Anti-IgE Antibodies.

A strategy was developed to obtain univalent F(ab) fragments against IgE, which would interfere with IgE-mediated activation of target cells, but lacked their activity due to cross-linking of IgE bound to Fc(epsilon)-receptors. Two kinds of mouse anti-human IgE monoclonal antibodies (mAb) against CH(2) or CH(3) domains induced histamine release from basophils of allergic patients and healthy donors. F(ab')(2) fragments of the mAb (0.01 - 10.0 &mgr;g/ml) possessed the same activity. On the contrary, F(ab) fragments of the mAb did not activate basophils, but in concentrations up to 10.0 &mgr;g/ml they inhibited, both in direct and cross reaction, histamine secretion induced by anti-IgE mAb and their F(ab')(2) fragments. Allergen-induced histamine release from basophils of pollen-sensitive patients was also inhibited by F(ab) fragments of anti-IgE mAb. It was suggested that univalent F(ab) fragments of anti-IgE mAb binding to cell-fixed IgE molecules modified their allergen-induced conformation and, as a result of that, inhibited mediator release from the cells.

Immunological properties of allergen chemically modified with synthetic copolymer of N-vinylpyrrolidone and maleic anhydride.

Several conjugates of model allergen ovalbumin (OA) and the copolymer of N-vinyl pyrrolidone and maleic anhydride (VMA) modified with epsilon-aminocaproic acid (Acp) were prepared in different OA/Acp-VMA ratios. All conjugates were separated by ultrafiltration and analyzed by HPLC. Their compositions were determined by amino acid analysis and UV spectrometry. To detect immunogenicity, all conjugates were injected intraperitoneally into (CBAxC57BL/6)F1 mice three times in 3-week intervals in OA doses equivalent to 0.5, 10, and 100 micrograms/mouse. Only the conjugate containing 20%OA (OA(20%)-Acp-VMA) did not induce significant quantities of anti-OA IgE, but did induce anti-OA IgG antibodies in dose-dependent manner comparable to that of unmodified OA. Mixtures of OA and Acp-VMA or OA modified only with VMA without Acp activation with Acp induced dose-dependent anti-OA IgE and IgG antibody formation comparable to that of OA. Using passive cutaneous anaphylaxis, RAST inhibition and leukocyte histamine release, a significant reduction of allergenicity was noted using OA(20%)-Acp-VMA. This conjugate stimulated activation of the OA-specific T-cell hybrid 3DO-548 comparable to that of unconjugated OA. During experimental allergen-specific hyposensitization with OA(20%)-Acp-VMA, suppression of anti-OA IgE response and elevation of anti-OA IgG responses were noted when compared with unmodified OA. Selective blockade of B-cell epitopes of allergen may occur using the carrier Acp-VMA to reduce allergenicity while not affecting T-cell epitopes, thereby preserving immunogenicity. This approach of chemical modification of allergen suggests new opportunities in the creation of preparations for allergen-specific immunotherapy.

[A shock reaction from insect bites in patients with urticaria pigmentosa]. / Shokovaia reaktsiia pri uzhalenii nasekomym u bol'nykh pigmentnoi krapivnitsei.

The examination of 11 urticaria pigmentosa (UP) patients included allergological history, skin prick, scarification tests and intracutaneous tests with noninfectious and bee poison allergens, total and specific serum IgE measurements, in vitro reaction of histamine release from peripheral blood basophils induced by bee poison. The response of mastocytosis patients to insect sting was characterized by a rapid (within 5 min) development of severe systemic reactions or shock. The skin reactions and serum antibodies to bee poison were not registered in 9 of 11 patients. They also had a negative reaction of allergen-specific histamine release from basophils. This gives evidence for nonimmunological, pseudoallergic mechanism of the shock reaction. The latter can be prevented by bee poison immunotherapy. IgE-antibody-mediated allergic reaction to bee sting could not be excluded in 2 patients. For them specific immunotherapy with bee poison, possibly with purified poison preparations containing the allergens alone, are indicated.

Histamine releasing activity of blood mononuclear cells is acquired by means of activation of mast cells.

It has been shown that peripheral blood mononuclear cells (PBMC) obtained from atopic patients with acute clinical manifestations of pollinosis, atopic dermatitis or bronchial asthma, and preincubated in vitro for 18 hours, acquired the ability to induce histamine release from auto-basophils and basophils of healthy donors. Both PBMC and their supernatants possessed this histamine releasing activity (HRA). During remission, HRA could be reproduced in sensitive patients after positive cutaneous tests with a specific allergen. Skin tests with non-specific allergen or histamine-induced provocations were ineffective. HRA of PBMC was also reproduced in healthy individuals after pronounced Prausnitz-Küstner reactions or compound 48/80-induced inflammatory responses. It is concluded that the in vivo activation of mast cells (MC) might be responsible for the acquirement by PBMC of the potential ability to induce histamine release and that this ability was realized after in vitro incubation of such prepared PBMC.

[A comparative study of the efficacy of Tilade and intal in atopic bronchial asthma]. / Sravnitel'noe izuchenie éffektivnosti taileda i intala pri atopicheskoi bronkhial'noi astme.

The authors compared the responses of patients with atopic asthma to two cromolyn drugs of different generations, tilade and intal. As shown by clinical, allergological and immunological findings, tilade (sodium nedocromil) compared to intal is more active against atopic bronchial asthma complicated by obstructive bronchitis. It can more efficiently reduce specific and nonspecific bronchial hyperreactivity, is more potent against inflammation. Due to tilade, the need in glucocorticoid inhalation lowered, it became possible to induce a prolonged remission.