Sulfated polysaccharides from Delesseria sanguinea (Hudson) Lamouroux inhibit the release of inflammatory cytokines in vitro

Sulfated polysaccharides (SP) like the prime example heparin are known to exhibit a wide range of biological activities. Unfractionated heparin (UFH) was shown to significantly attenuate the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by human polymorphonuclear neutrophils (PMN) and monocytes (MC) in vivo and in vitro [1,2], and thus to inhibit an important step of inflammatory processes.

The aim of this study was to investigate whether also SP extracted from Delesseria sanguinea inhibit the cytokine release in vitro. Furthermore, the influence of the extraction method (aqueous extract or alkaline extract) on these effects was examined. Reference substances were UFH and PS3 (a semisynthetic β-1, 3 glucan sulfate (US7008931-B2) with proven anti-inflammatory activity in vivo.

PMN and MC isolated from blood of healthy volunteers were activated with LPS in presence or absence of increasing concentrations of the test compounds. The concentrations of TNF-α, IL-6 and IL-8 in the cell supernatant were quantified by ELISA.

The SP from D.s. showed a conc.-dependent (0.005–1µg/ml) reduction by up to 70% of the LPS-induced release of

TNF-α and IL-6 by MC and PMN as well as of IL-8 by MC. They were as active as PS3 and superior to UFH. Further, the inhibition by SP extracted with water was stronger than that by SP extracted with NaOH. By control experiments, both any influence on the cytokine measurement by ELISA and any effect on non-stimulated cells could be excluded.

In conclusion, the SP isolated from D.s. reduce the cytokine release by stimulated PMN and MC. This activity and further in vitro effects like inhibition of complement activation, elastase and hyaluronidase suggest an anti-inflammatory potential.

Acknowledgements: this project is financed by the EU (FIAF/EFF) and the LFALF Mecklenburg-Vorpommern

References: [1] Anastase, S. et al. (2003) J. Biomed. Mater. Res. 66: 376–84 [2] Masihi, et al. (1997) Int. J. Immunopharmac. 19: 463–468