Effect of the synthetic regulatory peptide thymohexin on the production of various classes of immunoglobulins

Abstract

Some mechanisms of the immunoregulatory effect produced by the new drug thymohexin (immunophan), which contains synthetic hexapeptide as a pharmacological agent, are studied. Administration of the drug in a culture of polyclonally activated mononuclear cells from healthy donors intensifies IgM, IgG, and IgA production and inhibits IgE synthesis. Treating intact mononuclear cells with thymohexin does not significantly affect the production of immunoglobulins. The drug is found to intensify IgA synthesis in cases of genetically determined insufficiency and to suppress the production of IgE by lymphocytes in patients with atopic dermatitis. The immunoregulatory effect of the drug is shown to be mediated via cell-cell interaction in the system of transfer of thymohexin-activated mononuclears. Key Words: thymohexin; mononuclears; immunoglobulins; regulatory cells; atopic dermatitisRecent achievements in the design of drugs for the correction of disorders in the immune system are mainly due to the discovery of thymic regulatory peptides. Based on individual representatives of these peptides, such second-generation drugs as thymosin a 1 and some others have been developed and are now being used clinically for the treatment of a number of disorders accompanied by alterations in T-cell immunity [7,9]. However, the second-generation drugs have not found wide application due to complications in synthesis technology as well as to the polyfunctional properties of thymus regulatory peptides.Immunocorrective peptides of the third generation, containing synthetic short fragments of thymus regulatory peptides, are now being proposed [5]. Meanwhile, further search for active peptide fragments is exhausted due to the limited assortment of natural re~atory peptides of the central immune organs.Obtaining modified synthetic regulatory peptides or peptide drugs of the fourth generation may Central Research Institute of Epidemiology; Medicogenetic Research Center of the Russian Academy of Medical Sciences; Bionoks Biotechnology Conglomerate, Moscow be one of the possible ways of enlarging the arsenal of immunocorrectives, including those for the treatment of congenital and acquired immune disorders. To this end, a hexapeptide of original structure has been obtained as the pharmacological agent of a new fourth-generation drug, thymohexin (TH) (immunophan). Limited clinical trials have proved its positive effect on the production of specilic antibodies in patients with chronic brucellosis as well as an achievement of seroconversion in patients with chronic viral hepatitis B [4,8].A study of the effect of TH on the synthesis of different classes of immunoglobulins (Ig) by mononuclear cells (MNC) of healthy donors and patients with noninfectious pathology was undertaken to assess the mechanism of action of TH and the sphere of its use. MATERIALS AND METHODSMNC isolated in a Ficoll-Vero~aphin density gradient from heparinized peripheral blood were obtained from healthy donors and from atopic der-0007-4888/94/0010-I 117512.50 9Plenum Publishi...

Imunofan—RDKVYR Peptide—Stimulates Skin Cell Proliferation and Promotes Tissue Repair

“…IM has been reported to be a compound with in vivo immunoregulatory properties, for example it has been reported to increase the production of IgM, IgG, and IgA in human lymphocyte cultures and to suppress the synthesis of IgE. However, IM has been found to induce the production of immunoglobulins following stimulation with pokeweed mitogen but no influence has been observed without pre-treatment of lymphocytes with the mitogen [ 38 ]. Our studies were conducted in vitro on isolated PBMCs and indicated that IM did not activate the immune system (no activation of CTL, Th, and NK lymphocytes), thus suggesting IM is safe for use.…”