N A Konoplia’s research while affiliated with National Academy of Sciences of Belarus and other places

The immunotropic activity of three derivatives of docosahexaenic acid (N-docosahexaenoyl-L-serine phosphate, N-docosahexaenoyl-L-threonine phosphate, and N-docosahexaenoyl-L-tyrosine phosphate) in complexes with high-purity human alpha-fetoprotein was evaluated. The polyene compounds stimulate the humoral immunity in mice immunized with T-dependent antigen (ram red blood cells). The immunotropic activity of the alpha-fetoprotein-ligand complexes studied depends on the structure and the content of polyene ligands.

The immunopharmacological properties of two new compounds with an 8-azasteroidal structure, representing the salts (hydrochloride and acetate) of 12-imino-substituted 8-aza-D-homogonan, were studied in comparison with the properties of the immunostimulant trimeson. Similar to trimeson, both new compounds produce a dose-dependent activation of the humoral chain of immunogenesis in the model of primary immune response to goat erythrocytes in CBA, C57BL/6, and C57W mice. The immunostimulant activity of the 8-aza-D-homogonan derivatives is inversely proportional to the antigen load (2 x 10(7)-2 x 10(9) goat erythrocytes per mice) and depends to a considerable extent of the genotype of experimental animals. A modification of the 8-aza-D-homogonan structure by substituting imino group for oxygen at position 12 of the 8-azasteroidal skeleton leads to a sharp increase in toxicity as compared to that of trimeson.

The effect of the immunostimulator trimeson of the 8-aza-gomogonan series on the cells of the mononuclear monocyte system was studied in C3H and ICR mice in vitro. Intraperitoneal injection of trimeson (50 mg/kg 1 x 10(-7)-1 x 10(6) M) inhibits, as a rule, the initial stages of the phagocytizing process but stimulates the bactericidal properties of the peritoneal phagocytes and their mechanisms of processing and destruction of the antigen material. In the system of adaptive transfer of donor splenocytes and peritoneal macrophages to recipients exposed to lethal radiation, trimeson (20 mg/kg intravenously, 50 mg/kg per os) increases the immunogenic function of the mononuclear phagocytes in formation of the primary immune response to sheep erythrocytes.

It was shown that a phytosteroid ecdisterone which is the principle of a new tonic drug ecdisten in doses of 5-20 mg/kg is able to stimulate the primary immune reaction slightly effecting the indices of T-cell immunity activity and phagocyte functions. On increasing ecdisterone dose to 50 mg/kg inhibition of the number of antibody cells in the mouse spleen was marked.