Alleviation of Experimental Septic Shock in Mice by Acidic Polysaccharide Isolated from the Medicinal Mushroom Phellinus linteus
Biological and Pharmaceutical Bulletin
This study reports that acidic polysaccharide (PL) isolated from Phellinus linteus alleviated the septic shock induced by high dose lipopolysaccharide (LPS) injection in mice. To examine the origin of this effect, we investigated cytokine production in serum and the expression of MHC II in B cells and macrophages in areas of inflammation. Pretreatment with PL 24 h before LPS administration resulted in a significant inhibition of up to 68% of circulating tumor necrosis factor (TNF)-a a, a
... (TNF)-a a, a moderate reduction of 45% of interleukine (IL)-12 and 23% of IL-1b b, but no significant reduction in IL-6. In addition, the expression of MHC II in B cells and macrophages was examined. Our results show that LPS-stimulated cytokine release and the level of MHC II can be modulated by in vivo administration of soluble PL in mice. The decrease of IL-1b b, IL-12 and TNF-a a in sera and the downmodulation of MHC II during septic shock may contribute to the long survival of mice by PL. Administration of PL in vivo decreases IL-2, IFN-g g and TNF-a a production in splencotyes and enhances spontaneous cell apoptosis in macrophages and lymphocytes stimulated with LPS in vitro. Thus, part of the anti-inflammatory effects of PL treatment in vivo may result from the enhanced apoptosis of a portion of the activated macrophages and lymphocytes. The ability of PL to significantly reduce the TNF-a a production indicates the potential of the polysaccharides in possible therapeutic strategies that are based on down-regulation of TNF-a a.