Biological Activity of Peptide SCV-07 Against Murine Tuberculosis.
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.
Simbirtsev
Andrey
A
Cytokin Ltd., St.-Petersburg, Russia.
Kolobov
Alexander
A
Zabolotnych
Natalia
N
Pigareva
Natalia
N
Konusova
Valentina
V
Kotov
Alexander
A
Variouchina
Elena
E
Bokovanov
Vladimir
V
Vinogradova
Tatyana
T
Vasilieva
Svetlana
S
Tuthill
Cynthia
C
D000818:Animals; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4; D051379:Mice; D011446:Prospective Studies; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology
D032581:Tuberculosis Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma