Experimental bone marrow failure in mice ameliorated by OCH via tippling the balance of released cytokines from Th1 to Th2

Abstract

Background: OCH was reported to stimulate natural killer T (NKT) cells to produce predominantly T helper type 2 (Th2) cytokines. The present study was attempted to evaluate potential protection of OCH on acquired bone marrow failure syndromes (BMFS) in mice model.

Methods: BMFS in mice model was established by exposure to sublethal irradiation followed by infusion with 5 × 10(6) B6 lymph nodes cells. Mice were injected intraperitoneally (I.P.) with either OCH or α-galactosylceramide (α-GC) at a dose of 100 µg kg(-1) twice a week for two weeks after post-irradiation. The control mice were I.P. with vehicle alone (10% dimethyl sulfoxide in phosphate-buffered saline). Meanwhile, anti-interleukin-4 (anti-IL-4) monoclonal antibody (mAb) (500 µg/animal) was given I.P. 2 hours prior to vehicle or OCH administration. Both interferon-γ (IFN-γ) and IL-4 levels in the serum were measured by enzyme-linked immunosorbent assay. Colony-forming unit-granulocyte-macrophage (CFU-GM) by bone marrow (BM) mononuclear cells was counted. The percentage of NKT cell in BM cells and intracellular cytokines were determined by flow cytometry.

Results: The treatment of OCH in vivo decreased the IFN-γ/IL-4 ratio in the serum, and increased the transformation of NKT cells into NKT2 cells. The treatment of OCH in vitro increased the colonies of CFU-GM.

Conclusion: Our data suggests that OCH ameliorated immune-mediated BMFS in CByB6F1 mice via activation of NKT cells, and shifting the balance from Th1 to Th2.