Immunological response to (1,4)-alpha-D-glucan in the lung and spleen of endotoxin-stimulated juvenile rats.
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.
Velazquez
Ectis A
EA
Division of Critical Care Medicine, Miami Children's Hospital, Miami, FL, USA.
Kimura
Dai
D
Torbati
Dan
D
Ramachandran
Cheppail
C
Totapally
Balagangadhar R
BR
D000818:Animals; D019446:Endotoxemia / Q000276:immunology / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005936:Glucans / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D005936:Glucans; D007155:Immunologic Factors; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C044101:endotoxin, Escherichia coli; D007371:Interferon-gamma; C040088:1,4-glucan