Immunostimulatory Activity of Milife, A Novel Immunomodulator of Fungus Origin

Abstract

Milife is a novel immunomodulator derived from the fungus Fusarium Sambucium. In this study we examined immunomodulatory properties of Milife in 10 months-old BLRB mice. Milife was given to mice orally in a daily dose of 1 mg per mouse, for 2 to 6 days. Groups of mice were sacrificed on days 2, 4, and 6 of treatment, and 3 weeks after completion of a 6 days treatment with Milife, and lymphoid organs were obtained for analysis. Milife administration led to rapid and significant increase in total leukocyte and lymphocyte numbers in peripheral blood that persisted for at least 3 weeks after a 6 days treatment. Cellularity of lymph nodes, bone marrow and thymus increased significantly at days 4 and 6 of treatment, but returned to pretreatment levels after Milife discontinuation. Though total splenocyte numbers did not change dramatically, there occurred delayed increase in CD4⁺ cells in the spleen 3 weeks following treatment. Preferential accumulation of CD4⁺ cells was also consistently found in peripheral blood, with the peak being observed at day 6 of treatment. As a result, CD4/CD8 ratio in blood and spleen was significantly higher in treated than in untreated mice. Splenocytes from treated mice proliferated more vigorously in response to Con A. When added in vitro, Milife also mildly costimulated Con A- induced proliferation of Splenocytes from intact animals. In conclusion, we have found that Milife can stimulate leuko- and lymphopoesis in BLRB mice, in particular, accumulation of CD4⁺ T cells in peripheral lymphoid organs. We conclude that Milife may represent an immunomodulator with the potential to correct T cell dysfunction in patients with immunodeficiency.