ABSTRACT
Aqueous extracts from fruit bodies and mycelia of various higher Basidiomycetes were studied in search for reliable biological effects. In vitro and in vivo experiments were conducted. The results showed that the aqueous extracts demonstrated various types of marked biological actions: an increased production of reactive oxygen forms by neutrophil cells of human peripheral blood; a significant mitogenic activity in a wide range of concentrations; stimulation on production of inflammatory cytokines interleukine 1-beta and interleukine-8 by peripheral blood cells; a decrease in both average tumor size in mice with transplanted melanoma B16 and a manifestation of tumorous intoxication; and a prolongation in the survival rate of such mice.
Subject(s)
Adjuvants, Immunologic/pharmacology , Agaricales/chemistry , Antineoplastic Agents/pharmacology , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adjuvants, Immunologic/isolation & purification , Animals , Antineoplastic Agents/isolation & purification , Humans , Mice , Mice, Inbred CBA , Neoplasm Transplantation , Neutrophils/drug effects , Neutrophils/metabolism , Reactive Oxygen Species/metabolismABSTRACT
SCV-07 (gamma-glutamyl-tryptophan) is a new immunomodulatory compound that was developed and patented both for composition and immunomodulatory use. SCV-07 was shown to have a broad spectrum of immunostimulatory activities both in vitro and in vivo. In the present study we investigated the biological activity of SCV-07 in a murine model of experimental tuberculosis (TB) induced with M. bovis-bovinus 8 strain. Therapy with SCV-07 at doses of 0.01, 0.1, and 1 &mgr;g/kg (5 daily injections) decreased the lung damage index compared to untreated controls and to those treated with isoniazid alone. The growth of M. bovis-bovinus 8 in spleen culture was decreased. Cytokine studies showed that on the 24th day after the treatment with SCV-07 the production of IL-2 was restored to the level seen in uninfected animals. Proliferative responses for both thymic and spleen cells were nearly restored to the responses observed in uninfected animals. IFN-gamma production by both thymic and spleen cells, as well as its circulating levels in serum, was increased by the SCV-07 treatment. Concurrently, IL-4 production was decreased in the same cell types and the serum. These changes suggest that SCV-07 is stimulating a shift of T helper cells to a Th1-like immune response. SCV-07 treatment also stimulated the macrophage functions, which had been decreased by tuberculosis infection and isoniazid therapy, with an improved phagocytosis activity of peritoneal macrophage. The obtained results suggest that SCV-07 treatment increases the efficacy of anti-tuberculosis therapy as well as the strength of the immune response. Thus, SCV-07 is a prospective immunomodulator for a complex therapy of TB.
