Cytokine synthesis of human monocytes stimulated by triple or single helical conformer of an antitumour (1 -> 3)-beta-D-glucan preparation, sonifilan

It has been suggested that the immunopharmacological activity of soluble (1 -->3)-beta-D-glucan depends on it's conformation in mice. In this study, we examined the relationship between the conformation of Schizophyllan (SPG), a high molecular weight (1-->3)-beta-D-glucan, and cytokine productivity i n an in vitro human system. Monocyte-like human cell lines, THP-1 and U-937 , and peripheral blood mononuclear cells (PBMC) were used. THP-1 and U-937 cells were differentiated by phorbol myristate acetate (PMA) before use. SP G usually has a triple helical conformation in water, but it was modified b y treatment with aqueous sodium hydroxide to become a single helical confor mer (SPC-OH). SPG or SPG OH was added to the macrophage cell culture and ge ne expression and translation of several cytokines was analyzed by RT-PCR, ELISA, or bioassays. Differentiated THP-1 expressed high levels of cytokine genes, such as IL-8, in response to SPG-OH. High levels of IL-12 p70 were detected from THP-1 cells stimulated with SPG-OH. U-937 cells expressed hig h levels of IL 8 and TNF-alpha after SPG-OH treatment. Furthermore, PBMC is olated from healthy donors also strongly reacted with SPG-OH but not with S PG. High concentrations of TNF-alpha were detected in SPG-OH-stimulated PBM C cultures. These data suggest that the biological activities of SPG are st rongly associated with its conformation in humans.