Synergistic induction of lymphokine (IL-2)-activated killer activity by IL-2 and the polysaccharide lentinan, and therapy of spontaneous pulmonary metastases

Abstract

Spleen cells of C57BL/6N mice bearing lung metastases were induced to the cytotoxic state by subcutaneous injection of recombinant human interleukin-2 (IL-2) at a minimum dose of 5 x 10(4) U/mouse three times a day for 3 consecutive days. A single intraperitoneal injection of lentinan alone at concentrations of up to 10 mg/kg body weight did not render spleen cells cytotoxic to P-29 cells, but a combination of subthreshold doses of these agents (5 x 10(4) U/ml IL-2 and 5 mg/kg lentinan) induced significant in vivo lymphokine-activated killer activity in spleen cells of tumor-bearing mice. Similarly, spleen cells from mice treated i.p. with lentinan became cytotoxic on in vitro treatment with IL-2. The in vitro responsiveness of spleen cells to IL-2 was maximal 3 days after i.p. injection of lentinan. Synergism between IL-2 and lentinan was also observed in mice bearing spontaneous lung micrometastases: neither IL-2 (less than 5 x 10(4) U/mouse) nor lentinan (less than 2.5 mg/kg) alone had a therapeutic effect, but multiple injections of IL-2 with a single injection of lentinan resulted in significant inhibition of spontaneous pulmonary metastases. From these results we conclude that IL-2 and lentinan in combination are more effective than either one alone for inducing destruction of pulmonary metastases.

A new application of Trichoderma asperellum as an anopheline larvicide for eco friendly management in medical science

“…Similarly, earlier studies have reported that the spiracles of anopheline larvae are plugged due to the entry of fungal spores, causing larval death 39 , 40 . The head of the mosquito larvae is an equally important fungal infection site that supports our observation 41 . Further, we also observed that a few spores were attached to the body surface of the larvae and these spores germinated and penetrated through the larval cuticle, followed by vegetative fungal growth.…”

“…Methanolic extract exhibited larvicidal activity when applied to anopheline larvae. Since many of the compounds have been shown to act synergistically 41 , it is worth testing the cytotoxic and cell growth inhibitory effects of the whole fungal extract rather than its individual components. This principle (synergy) allows for stronger effects when used as a whole products, while quenching or nullifying any unwanted side-effects contributed to the presence of the individual components 42 .…”

Significant antitumor effect of a synthetic lipid A analogue, DT-5461, on murine syngeneic tumor models

“…Lentinan is a [31,3-glucan with ~1,6 branches that has been purified completely from Lentinus edodes, an edible mushroom in Japan and found to have characteristic immunomodulatory effects on T cells and to enhance the activities of some macrophages and NK cells in vivo [37]. These agents have been used for the therapy of cancer because of their potential value as biological response modifiers.…”

Bioactive Polysaccharides from TCM Herbs as Anti-Cancer Adjuvants

“…Naturally derived polysaccharides including heteroglycans and proteoglycans of certain molecular weight and structure have specific broad-ranged immunomodulatory properties which have been recognized for several decades. Such immunomodulating activity includes activation of macrophages (Adachi et al, 1990), monocytes (Czop and Austen, 1985a), natural killer cells (Peter et al, 1988), lymphocyte activated killer cells (Yamasaki et al, 1989), dendritic cells (Kim, 2007), tumor-infiltrating lymphocytes (Kariya et al, 1991) and other lymphocytes (Kumazawa et al, 1985). The stimulated release of various cytokines including interferons (Kandefer-Szerszen and Kawecki, 1973), interleukins (Sakagami et al, 1988), tumor necrosis factor (Abel and Czop, 1992) and colony stimulating factors (Hashimoto et al, 1990) have also been well documented.…”