An immune-modulating formula comprising whey peptides and fermented milk improves inflammation-related remote organ injuries in diet-induced acute pancreatitis in mice

Abstract

It has been demonstrated that an immune-modulating enteral formula enriched with whey peptides and fermented milk (IMF) had anti-inflammatory effects in some experimental models when it was administered before the induction of inflammation. Here, we investigated the anti-inflammatory effects of the IMF administration after the onset of systemic inflammation and investigated whether the IMF could improve the remote organ injuries in an acute pancreatitis (AP) model. Mice were fasted for 12 hours and then fed a choline-deficient and ethionine-supplemented diet (CDE diet) for 24 hours to induce pancreatitis. In experiment 1, the diet was replaced with a control enteral formula, and mice were sacrificed at 24-hour intervals for 96 hours. In experiment 2, mice were randomized into control and IMF groups and received the control formula or the IMF respectively for 72 hr or 96 hr. In experiment 1, pancreatitis was induced by the CDE diet, and inflammatory mediators were elevated for several days. Remote organ injuries such as splenomegaly, hepatomegaly, and elevation of the hepatic enzymes developed. A significant strong positive correlation was observed between plasma MCP-1 and hepatic enzymes. In experiment 2, the IMF significantly improved splenomegaly, hepatomegaly, and the elevation of hepatic enzymes. Plasma MCP-1 levels were significantly lower in the IMF group than in the control group. Nutrition management with the IMF may be useful for alleviating remote organ injuries after AP.

Keywords: acute pancreatitis; immune-modulating formula; inflammation; remote organ injury.

Fig. 1.

Experimental protocol. IMF: immune-modulating formula.

Fig. 2.

Plasma levels of inflammatory mediators in experiment 1. (A) TNF-α, (B) IL-6, and (C) MCP-1. Values are means ± standard deviations. ^†p<0.05, vs. −24 hr. ^‡p<0.01, vs. −24 hr.

Fig. 3.

Incidence of remote organ injury in experiment 1. (A) Liver and (B) spleen weights and plasma (C) AST and (D) ALT levels. Values are means ± standard deviations. ^†p<0.05, vs. −24 hr. ^‡p<0.01, vs. −24 hr.

Fig. 4.

Correlations between MCP-1 or IL-6 and AST or ALT in experiment 1.

Fig. 5.

Incidence of remote organ injuries in experiment 2. (A) Liver and (B) spleen weights and plasma (C) AST and (D) ALT levels. Values are means ± standard deviations. ^#p<0.1, vs. −24 hr. ^†p<0.05, vs. −24 hr. ^‡p<0.01, vs. −24 hr. *p<0.05, vs. control group. **p<0.01, vs. control group.

Fig. 6.

Plasma levels of inflammatory mediators in experiment 2. (A) TNF-α, (B) IL-6, and (C) MCP-1. Values are means ± standard deviations. ^†p<0.05, vs. −24 hr. ^‡p<0.01, vs. −24 hr. *p<0.05, vs. control group.

Fig. 7.

Correlations between MCP-1 and AST or ALT in experiment 2.