Inhibitory Effects of Carrageenans on Endotoxin-Induced Inflammation

Abstract

The inhibitory effects of carrageenans (CRGs) on lipopolysaccharide (LPS) induced inflammation in a mouse model of endotoxemia and in complex therapy of patients with enteric infections of Salmonella etiology were studied. The atomic force microscopy (AFM) examination of LPS and its mixture with CRGs showed that the LPS morphology is significantly changed under the action of κ- and κ/β-CRGs. CRGs were able to increase the synthesis of anti-inflammatory interleukin 10 (IL-10) in vitro, and, at low concentrations, their activity in the mixture with LPS was higher. The protective effect of CRGs against Escherichia coli LPS was studied in vivo by monitoring the biochemical and pathomorphological parameters. The κ- and κ/β-CRGs and food supplement "Carrageenan-FE" increased the nonspecific resistance of mice to E. coli LPS at the expense of the inhibition of processes of thymus involution, adrenals hypertrophy, thyroid atrophy, hypercorticoidism, glycogenolysis, and lactate acidosis. The estimation of the therapeutic action of food supplement Carrageenan-FE in complex therapy of patients with enteric infections of Salmonella etiology is given. Carrageenan-FE restores the system of hemostasis and corrects some biochemical indicators and parameters in the immune systems of patients. These results allow us to hope for the practical application of CRGs for lowering the endotoxemia level in patients under the development of the infectious process caused by Gram-negative bacteria.

Keywords: carrageenan; cytokines; enteric infections; lipopolysaccharide; macromolecular structure; nonspecific resistance to lipopolysaccharide; salmonellosis.

Figure 1

AFM topography images: (a) κ-CRG, 0.1 mg/mL; (b) κ/β-CRG, 0.1 mg/mL; (c) lambda-CRG, 0.1 mg/mL; and (d) LPS, 0.05 mg/mL.

Figure 2

AFM topography images of mixtures in ratio 2:1 w/w: (a) κ-CRG + LPS; (b) κ/β-CRG + LPS; and (c) λ-CRG + LPS.

Figure 3

TNF-α (a) and IL-10 (b) levels stimulated by E. coli LPS and carrageenans. Concentrations of samples: 10 µg/mL (white column), 1 µg/mL (black), 100 ng/mL (gray), 10 ng/mL (light gray), and 1 ng/mL (black-dot). Mean (±SD) contents of cytokine in serum are presented. Whole blood was obtained from five healthy subjects and incubated with the samples at different concentrations. The level of cytokines in serum of normal donors was considered as a negative control used for statistical significance calculation. * Differences between the samples and the control were significant, p < 0.05.

Figure 4

TNF-α (a) and IL-10 (b) levels stimulated by preliminary incubation cells with E. coli LPS (10 min), and then CRGs. Concentrations of samples: 10 µg/mL (white column), 1 µg/mL (black); 100 ng/mL (gray); 10 ng/mL (light gray), and 1 ng/mL (black-dot). Mean (±SD) contents of cytokine in serum are presented. The level of cytokines in serum stimulated by E. coli LPS (10 µg/mL) was considered as a control used for statistical significance calculation. * Differences between samples and the control were significant, p < 0.05.