The Effect of Drugs with α-Glutamyl-Tryptophan for Cytokine Secretion and Level of Surface Molecule ICAM-1 In Vitro.

The study of the molecular mechanisms underlying the action of immunomodulatory drugs is important for substantiating their therapeutic effect. In the present work, spontaneous and TNFα-induced secretion of IL-1α and IL-8 pro-inflammatory cytokines, as well as the level of the ICAM-1 adhesion molecule in EA.hy 926 endothelial cell culture and peripheral blood mononuclear cells of healthy donors, is studied using an in vitro model of inflammation in the presence of α-glutamyl-tryptophan (α-Glu-Trp) and Cytovir-3. The aim was to evaluate cellular mechanisms mediating the immunomodulatory effect of α-Glu-Trp and Cytovir-3 drugs. It was shown that α-Glu-Trp reduced TNFα-induced IL-1α production and increased TNFα-stimulated level of the ICAM-1 surface molecule of endothelial cells. At the same time, the drug reduced secretion of the IL-8 cytokine induced by TNFα and increased the spontaneous level of ICAM-1 in mononuclear cells. Cytovir-3 had an activating effect on EA.hy 926 endothelial cells and human peripheral blood mononuclear leukocytes. In its presence, there was an increase in the spontaneous secretion of IL-8 by endothelial and mononuclear cells. In addition, Cytovir-3 increased the level of TNFα-induced ICAM-1 on endothelial cells and increased the spontaneous level of this surface molecule on mononuclear cells. Suppression of stimulated production of pro-inflammatory cytokines under the action of α-Glu-Trp both separately and as a part of Cytovir-3 may determine its anti-inflammatory properties. However, an increased level of the surface ICAM-1 molecule indicates mechanisms that enhance the functional activity of these cells, which is equally important for the implementation of an effective immune response to infection and repair of damaged tissues during inflammatory response.

Role of aqueous medium in mechanisms underlying the influence of immunoactive peptides in ultralow doses.

The mechanism underlying the influence of peptides in ultralow doses is based on distant signal transduction from the ligand molecules to target cells by means of water solitons. Biological activity of synthetic immunoactive peptides in concentrations below 10(-18) M depends on their structural and conformational characteristics. The data on temperature dependencies of the near-infrared spectrum for solutions of these peptides are presented.

Possible involvement of aqueous medium in distant signal transmission from immunoactive dipeptides.

Possible involvement of aqueous medium in distant signal transmission to target cells through solitons without formation of the ligand-receptor complexes is discussed. Temperature dependence of IR spectra for dipeptide and amino acid solutions in the far and near IR regions are presented, which prove principal possibility of such processes.