Abstract

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.