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

Basic Clin Pharmacol Toxicol. 2009 Nov;105(5):301-6. doi: 10.1111/j.1742-7843.2009.00447.x. Epub 2009 Jul 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endotoxemia / immunology
  • Endotoxemia / metabolism
  • Endotoxins / pharmacology*
  • Female
  • Glucans / pharmacology*
  • Immunologic Factors / pharmacology*
  • Injections, Intraperitoneal
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Spleen / drug effects*
  • Spleen / immunology
  • Spleen / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Endotoxins
  • Glucans
  • Immunologic Factors
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • endotoxin, Escherichia coli
  • Interferon-gamma
  • 1,4-glucan