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 treatment in Japan. The mechanism of SPG mediated antitumor activity is thought to be via immune stimulation, which includes cytokine production, hematopoietic 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 antitumor activity. To demonstrate the mechanism several parameters were examined using a high dose of SPG administration as follows: i) the effect on vascular permeability in vivo, ii) the priming effect on tumor necrosis factor (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 antibody production remained unchanged, but TNF-alpha production and adherence to a plastic plate was significantly reduced by a high dose of SPG. These facts strongly suggested that modulation of the cytokine syntheses and the leukocyte traffic would be the causative mechanisms of the failure of antitumor activity by an overdose of SPG.
Miura
T
T
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Miura
N N
NN
Ohno
N
N
Adachi
Y
Y
Shimada
S
S
Yadomae
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005122:Exudates and Transudates / Q000166:cytology; D016209:Interleukin-8; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012510:Sarcoma 180 / Q000188:drug therapy; D012566:Sizofiran / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D012566:Sizofiran