A selective H4R antagonist prevents antigen-induced asthma-like reaction and airway inflammation in guinea pigs

Objective:  Curdlan, an extracellular bacterial polysaccharide, is a linear β-1,3-glucan. Previously, we developed Curdlan-oligo (CRDO). We investigated its effect on the production of cytokines in leukocytes from mice, and compared its activity with that of SCG, a 6-branched 1,3-β-glucan. Methods:  Splenocytes from DBA/2 mice were cultured with CRDO or SCG (0, 1, 10 or 100 μg/ml) in vitro, and then the supernatants were collected to measure cytokines. Bone marrow-derived dendritic cells (BMDCs) were cultured with CRDO (0, 1, 10 or 100 ng/ml) in vitro, and then the supernatant was collected to measure cytokines. Results:  SCG stimulated splenocytes in DBA/2 mice to produce GM-CSF, IFN-γ and TNF-α. CRDO induced production of GM-CSF and IFN-γ, but not TNF-α. The amounts of GM-CSF and IFN-γ were small compared with those produced in response to SCG. The effect of SCG on TNF-α production was partially inhibited by CRDO. In bone marrow-derived dendritic cells, CRDO induced production of TNF-α and IL-6. Conclusion:  Taken together, these results suggest that CRDO stimulated mouse leukocytes to induce the production of cytokines, and the mechanism of the effect of CRDO on leukocytes is different from that of SCG. Received 30 June 2008; returned for revision 5 August 2008; received from final revision 3 September 2008; accepted by A. Bauhofer 22 September 2008