ENHANCEMENT OF LPS TRIGGERED TNF-ALPHA (TUMOR-NECROSIS-FACTOR-ALPHA) PRODUCTION BY (1-]3)-BETA-D-GLUCANS IN MICE

Effects of (1-->3)-beta-D-glucans on tumor necrosis factor-alpha (TNF-alpha) production in mice in vivo were investigated with or without triggering stimulation of lipopolysaccharide (LPS). Administration of grifolan (GRN) (100-250 mu g/mouse) obtained from Grifola frondosa, did not elevate the TNF-alpha concentration in serum, but significantly elevated LPS (10 mu g/mouse)-elicited TNF-alpha production in serum. The priming effect was observed as early as 2h after administration and remained high for 3 weeks. The priming effect was dependent on the strain of mice, i.e. ICR, BALB/c, and MRL/lpr (15 weeks old) shelved high response. In addition, GRN administration increased membrane-bound TNF-alpha assessed by Western blotting and flow cytometry. Comparing the activity using structurally related glucans obtained from other microorganisms, highly branched glucans, SSC isolated from Sclerotinia sclerotiorum IFO 9395 and OL-2 from Omphalia lapidescence significantly increased TNF-alpha production. Small molecular weight GRN derivatives prepared by heat degradation method showed weaker priming effect. These facts suggested that the glucans showed priming effect of TNF-alpha production in vivo and that this effect was related to the degree of branching and molecular weight.