Abstracts Category : Other

Effects of fractions and compounds from marine invertebrates on immune responses

by rir skarsson Jn

Natural products are a productive and well recognized source of new therapeutics and much recent interest has been on exploring the vast biodiversity of marine organisms in search of novel bioactive compounds. The pathobiology of an array of autoimmune and inflammatory disorders is characterized by dysregulation of immune responses, leading to a chronic state of inflammation. Modulation of immune responses by bioactive natural compounds could, therefore, be of therapeutic value in the treatment of pathological inflammation. Antigen presenting cells (APCs), in particular dendritic cells (DCs), are capable of polarizing T cells towards specific effector phenotypes dependent on the nature of their activation and are a prime target for evaluating immunomodulating effects of natural compounds in the search for effective immunotherapeutic agents.The aim of this study was to identify and isolate anti-inflammatory compounds from marine invertebrates using a bioassay-guided isolation procedure and characterize the immunomodulatory effects of obtained bioactive fractions/compounds on DCs and DC mediated T cell activation. Human monocyte-derived DCs were matured and activated by lipopolysaccharide (LPS), tumour necrosis factor (TNF)- and interleukin (IL)-1 and cultured in the presence of fractions/compounds from the sponge (Porifera) Halichondria sitiens (H. sitiens) for 24 h. The effects of fractions/compounds on DC maturation was evaluated by the expression of the antigen-presentation and co-stimulation molecules CD86 and HLA-DR, respectively, and the anti-inflammatory properties were evaluated by measuring concentrations of the pro-inflammatory cytokines IL-12p40 and IL-6 and the anti-inflammatory/regulatory cytokines IL-10 and IL-27. The effects of H. sitiens fractions on DC mediated T cell activation was evaluated by measuring secretion of T helper (TH) cell specific cytokines, interferon (IFN)- (TH1), IL-13 (TH2), IL-17 (TH17) and IL-10 (regulatory T cell, Treg), by allogeneic CD4+ T cells activated by DCs which had been treated with selected bioactive fractions.Fractionation of H. sitiens resulted in a number of bioactive fractions but not in the isolation of pure bioactive compounds. The bioactive fractions contained mostly lipid compounds and had different effects on cytokine secretion by DCs, reducing and/or enhancing secretion of pro- and anti-inflammatory cytokines, respectively. The H. sitiens fractions did not affect maturation of the DCs, as was evident by unaltered expression of the surface molecules, CD86 and HLA-DR. These molecules are important for effective activation of T cells and DCs matured in the presence of fractions from H. sitiens are, therefore, expected to have unimpaired T cell activation capacities. Most of the bioactive fractions inhibited secretion of the pro-inflammatory cytokines IL-12p40 and IL-6 and two fractions enhanced secretion of the anti-inflammatory cytokine IL-10. Furthermore, allogeneic CD4+ T cells activated by DCs treated with fraction B3b3-J, which reduced IL-12p40 and IL-6