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Basic and Clinical Pharmacology and Toxicology 2009-Nov

Immunological response to (1,4)-alpha-D-glucan in the lung and spleen of endotoxin-stimulated juvenile rats.

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Ectis A Velazquez
Dai Kimura
Dan Torbati
Cheppail Ramachandran
Balagangadhar R Totapally

Keywords

Abstract

We investigated the effects of (1,4)-alpha-D-glucan (alpha-DG), a novel immune stimulatory drug from Tinospora cordifolia, on the concentration of pro- and anti-inflammatory cytokines (interleukin [IL]-1beta, IL-6, tumour necrosis factor-alpha [TNF-alpha], gamma-interferon [IFN-gamma] and IL-10) in the lung and spleen of endotoxin-stimulated juvenile rats. Experimental groups (n = 16/group) included controls with an intraperitoneal injection of saline, endotoxaemic rats with a non-lethal dose of 10 mg/kg Escherichia coli endotoxin, and endotoxaemic rats treated with two doses of 10 mg/kg alpha-DG, intraperitoneally, 2 and 4 hr after endotoxin injection. At 24 hr of treatment, rats were euthanized and lungs and spleen were removed for cytokines determination and lung injury. Endotoxaemia increased IL-1beta concentration by fivefold in both organs, while creating a moderate pulmonary hypercellularity (demonstrated by about 11% increase in the alveolar-septal thickening and 11% decrease in the alveolar-interstitial space ratio). In the lung, alpha-DG treatment reduced concentrations of IL-1beta by 30% (p > 0.05), IL-6 by 43% (p < 0.01), IFN-gamma by 46% (p < 0.01) and the anti-inflammatory cytokine, IL-10, by 31% (p > 0.05) compared to endotoxaemia. In the spleen, alpha-DG treatment decreased the ratio of IL-1beta to IL-10 by 55% (p < 0.05), demonstrating an anti-inflammatory trend. These data suggest that alpha-DG differentially modulates cytokine response in the lung and spleen and modifies the pro- and anti-inflammatory balance during an early period of endotoxaemia in juvenile rats.

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