Turmeric (Curcuma longa) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.

Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1β, IL-12p70 and IL-10 in human macrophages.

A total of forty weaned pigs ((Landrace×Yorkshire)×Duroc) were used to evaluate the effects of Lactobacillus acidophilus on inflammatory activity after lipopolysaccharide (LPS) challenge. Experimental treatments were as follows: (T1) control diet+saline challenge; (T2) control diet with 0·1 % L. acidophilus+saline challenge; (T3) control diet+LPS challenge; and (T4) control diet with 0·1 % L. acidophilus+LPS challenge. On d-14, piglets were challenged with saline (T1 and T2) or LPS (T3 and T4). Blood samples were obtained at 0, 2, 4, 6 and 12 h after being challenged and analysed for immune cell cytokine production and gene expression pattern. The L. acidophilus treatment increased the average daily weight gain (ADWG) and average daily feed intake (ADFI) compared with the control diet. With the control diet, the LPS challenge (T3) increased the number of immune cells and expression of TNF-α and IL-6 compared with the saline challenge (T1). Whereas with the saline challenge L. acidophilus treatment (T2) increased the number of leucocytes and CD4 compared with the control diet (T1), with the LPS challenge L. acidophilus treatment (T4) decreased the number of leucocytes, lymphocytes, CD4+ and CD8+ and expression of TNF-α and IL-6 compared with the control diet (T3). L. acidophilus treatment decreased the expression of TRL4 and NF-κB in peripheral blood mononuclear cells (PBMC) after LPS challenge, which leads to inhibition of TNF-α, IFN-γ, IL-6, IL-8 and IL1B1 and to induction of IL-4 and IL-10. We suggested that L. acidophilus improved ADWG and ADFI and protected against LPS-induced inflammatory responses by regulating TLR4 and NF-κB expression in porcine PBMC.

The aim of this study was to compare low doses of microencapsulated v. pharmacological ZnO in the diet of piglets on growth performance, ileum health status and architecture. One hundred and forty-four piglets weaned at 28 days and divided in 36 pens (two males and two females per pen), received a basal diet (control, Zn at 50 mg/kg) or the basal diet with ZnO at 3000 mg/kg (pZnO), or with lipid microencapsulated ZnO at 150 or 400 mg/kg (mZnO-300 and mZnO-800, respectively). After 14 and 42 days, three pigs per sex per treatment were euthanized to collect the ileum mucosa for immunohistochemistry, histomorphology, inflammatory cytokines and tight junction components gene expression. Data were analyzed with one-way ANOVA. At 0 to 14 days, the pZnO and mZnO-800 groups had greater average daily gain compared with control (P<0.05). Gain to feed ratio (G:F) in the same time interval was higher in pZnO group compared with control thus resulting in higher BW (P<0.05). At day 14, ileum villi height in mZnO-800 pigs was 343 µm v. 309 and 317 µm in control and pZnO, respectively (P<0.01) and villi:crypts ratio (V:C), as well as cells positive to proliferating cell nuclear antigen (PCNA), were greater in all treated groups compared with control (P<0.01). In mZnO-800 group, interferon-γ mRNA was the lowest (P=0.02), and both pharmacological ZnO and mZnO reduced tumor necrosis factor-α protein level (P<0.0001). Compared with pZnO group, mZnO-800 increased occludin and zonula occludens-1 protein level (1.6-fold and 1.3-fold, respectively; P<0.001). At day 42, both groups receiving microencapsulated ZnO had 1.7 kg greater BW than control and did not differ from pZnO group (P=0.01); ileum villi height and V:C ratio were the greatest for pZnO compared with the other groups, whereas PCNA-positive cells were the most numerous in mZnO-800 group (P<0.001). In conclusion, pigs receiving low doses of microencapsulated ZnO had G:F comparable with those receiving pharmacological level of ZnO in the overall post-weaning phase. Moreover, in the first 2 weeks post-weaning, microencapsulated ZnO effect on inflammatory status and ileum structure and integrity was comparable with pharmacological ZnO.

The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P< 0·05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8–24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

In the present study, a 2 × 2 factorial arrangement was conducted to investigate the effect of maternal supplementation with seaweed extracts ( − SWE v. +SWE, n 20) from day 83 of gestation until weaning (day 28) on post-weaning (PW) growth performance, faecal score, faecal enterotoxigenic Escherichia coli (ETEC) toxin quantification, intestinal histology and cytokine mRNA of unchallenged and ETEC-challenged pigs. Pigs were ETEC challenged on day 9 PW. There was a maternal treatment × challenge (SWE × ETEC) interaction effect on growth performance and faecal score (P< 0·05). Pigs from SWE-supplemented sows and ETEC-challenged (SE) had higher average daily gain (ADG) during 0–13 d PW and reduced faecal score during 0–72 h post-challenge than those from basal-fed sows and ETEC-challenged (BE) (P< 0·05). However, there was no difference between unchallenged pigs from the SWE-supplemented sows (SC) and basal-fed sows (BC) (P>0·10). Pigs from the SWE-supplemented sows had reduced heat-labile enterotoxin gene copy numbers than those from the basal-fed sows (P< 0·05). Maternal SWE supplementation increased the villus height in the ileum of pigs (P< 0·05). There was a SWE × ETEC interaction effect (P< 0·05) on IL-6 mRNA and a SWE × gastrointestinal (GI) region interaction effect (P< 0·05) on transforming growth factor-β1 (TGF-β1) and TNF-α mRNA. IL-6 mRNA was down-regulated in SC pigs than BC pigs (P< 0·05). However, there was no difference in IL-6 mRNA between SE and BE pigs. The mRNA of TGF-β1 and TNF-α was down-regulated in the colon of pigs from the SWE-supplemented sows compared with those from the basal-fed sows (P< 0·05). However, there was no difference in TGF-β1 and TNF-α mRNA in the ileum between the pigs from the SWE-supplemented sows and basal-fed sows. In conclusion, maternal SWE supplementation improves ADG and the aspects of GI health of weaned pigs following an ETEC challenge.

Vitamin D has been recognised as a potent immunomodulator and its deficiency is common in different population groups including patients with diabetic foot infection. Diabetic foot infection reflects the altered immune status of the host. As cytokine regulation plays a significant role in infection and wound-healing processes, the present study aimed to evaluate the association between vitamin D status and inflammatory cytokine profiles in patients with diabetic foot infection. The serum concentrations of vitamin D (25-hydroxyvitamin D), IL-1β, IL-6, TNF-α and interferon-γ (IFN-γ) were measured in 112 diabetic foot infection cases and 109 diabetic controls. Severe vitamin D deficiency (25-hydroxyvitamin D concentration < 25 nmol/l) was more common in cases than in controls (48·2 v. 20·5 %). Although age, duration of diabetes, HbA1C (glycosylated Hb) concentration and BMI were similar, cases had significantly higher concentrations of IL-6 (P≤ 0·001), IL-1β (P≤ 0·02) and TNF-α (P≤ 0·006) than controls. A significant negative correlation was also observed between 25-hydroxyvitamin D concentration and circulating concentrations of IL-1β (r − 0·323; P≤ 0·001) as well as IL-6 (r − 0·154; P≤ 0·04), but not between 25-hydroxyvitamin D and TNF-α and IFN-γ concentrations. Furthermore, a significant difference in IL-1β (P≤ 0·007) and IL-6 (P≤ 0·02) concentrations was observed in patients with severe 25-hydroxyvitamin D deficiency compared with patients with 25-hydroxyvitamin D concentration ≥ 25 nmol/l, and this difference was remarkable for TNF-α. In conclusion, severe vitamin D deficiency is associated with elevated inflammatory cytokine concentrations in diabetic patients, particularly in those with foot infection. A 25-hydroxyvitamin D concentration value < 25 nmol/l is suggested as the ‘cut-off’ for such immunological alterations in patients with diabetes mellitus.

Bioactive milk proteins may be important in protecting preterm infants from developing inflammation and necrotising enterocolitis (NEC). A preterm pig model was used to investigate the protective effects of enteral bovine lactoferrin (bLF) against NEC development and inflammation. Caesarean-delivered preterm pigs were fed parenteral and minimal enteral nutrition for the first 2 d followed by 2 d of total enteral nutrition before euthanasia. Pigs were stratified into two groups and fed with either a control formula (CON, n 15) or a 10 g/l of bLF-enriched formula (LF, n 13). NEC incidence, gut functions and inflammatory cytokines were analysed. NEC incidence and nutrient absorption were similar between the two groups. In pigs that developed NEC, disease outcome was more severe in the colon accompanied by increased intestinal permeability in LF pigs. In contrary, the LF pigs had a lowered IL-1β level in the proximal small intestine. Dose-dependent effects of bLF on cell proliferation, intracellular signalling and cytokine secretion were tested in porcine intestinal epithelial cells (PsIc1) in vitro. Low doses (0·1–1 g/l) increased cell proliferation via extracellular signal-regulated kinase (ERK), limited IL-8 secretion and prevented NF-κB and hypoxia-inducible factor-1α (HIF-1α) activation, suggesting anti-inflammatory effects. In contrast, at a higher dose (10 g/l), bLF exerted adverse effects by reducing cell proliferation, stimulating IL-8 release, inhibiting ERK activation and up-regulating NF-κB and HIF-1α activation. Overall, at a dose of 10 g/l, bLF exacerbated disease severity in pigs that developed NEC, while the in vitro studies indicated the positive effects of bLF at low doses (0·1–1 g/l). Supplementation of infant formulas with bLF should therefore be optimised carefully.

Aging is associated with increased intestinal inflammation and elevated risk of chronic diseases including inflammatory bowel diseases and colon cancer; many epidemiologic studies show that regular exercise reduces risk. This study examined the effects of long-term voluntary exercise on inflammatory mediators expressed in the intestine of older (15–16 months), healthy C57BL/6 mice. Animals were assigned to four months of freewheel running (WR; n = 20) or to a “sedentary” no wheel running (NWR; n = 20) control group. Intestinal lymphocytes were harvested and analysed for expression of (1) pro-inflammatory (TNF-α, IL-1β) and pleiotropic (IL-6) cytokines, and (2) pro-(caspase-3/-7) and anti-(Bcl-2) apoptotic proteins. Training was confirmed by skeletal muscle enzyme activity; stress was assessed by plasma 8-iso-PGF2α and corticosterone. The WR mice had a lower expression of TNF-α, caspase-7, and 8-isoprostanes (p < .05) compared to sedentary controls, suggesting that long-term exercise may “protect” the bowel by reducing inflammatory cytokine and apoptotic protein expression.