Failure in antitumor activity by overdose of an immunomodulating beta-glucan preparation, Sonifilan

Schizophyllan (SPG, Sonifilan) is a soluble (1-->3)-beta-D-glucan, used as a biological response modifier (BRM) with radiation therapy for cancer trea tment in Japan. The mechanism of SPG mediated antitumor activity is thought to be via immune stimulation, which includes cytokine production, hematopo ietic response, and so on, In this paper, we found that the activity of SPG was quite long-lived and an overdose significantly failed to display the a ntitumor activity. To demonstrate the mechanism several parameters were exa mined using a high dose of SPG administration as follows: i) the effect on vascular permeability in vivo, ii) the priming effect on tumor necrosis fac tor (TNF-alpha) production in vivo, iii) the effect on macrophage adherence to plastic plate in vitro, and iv) anti-Sarcoma 180 antibody production in vivo. It was evident that vascular permeability and anti-Sarcoma 180 antib ody production remained unchanged, but TNF-alpha production and adherence t o a plastic plate was significantly reduced by a high dose of SPG, These fa cts strongly suggested that modulation of the cytokine syntheses and the le ukocyte traffic would be the causative mechanisms of the failure of antitum or activity by an overdose of SPG.