Stimulation of multiple cytokine production in mice by alginate oligosaccharides following intraperitoneal administration.

We previously reported that alginate oligomers, prepared by specific enzymatic digestion of alginate polymer, induced cytokine secretion from mouse macrophage cell line RAW264.7. In the present study, we examined the cytokine levels in the mouse serum after intraperitoneal (ip) administration of a mixture of alginate oligomers. After ip injection of 700 mg/kg of oligomers, the serum level of G-CSF increased promptly and reached the maximum level after 2 h and this high level was sustained until 6 h, and then gradually decreased, whereas injection of 700 mg/kg of alginate polymer had no effect. The effect of alginate oligomer mixture was dose-dependent, and 70 mg/kg was sufficient to attain the maximum serum level of G-CSF. A Bio-Plex bead assay that can detect 23 cytokines at the same time revealed that ip administration of alginate oligomer mixture induced an increase in 20 cytokines in the serum at different levels and with different kinetics depending on the cytokine. Among the cytokines detected the level of G-CSF was the highest. The levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, keratinocyte-derived chemokine (KC), IL-12 (p40), and regulated upon activation normal T cell expressed and secreted (RANTES) were also relatively high and exceeded 5000 pg/mL serum at the peak point.