Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain ω-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (ω-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.

Although it is known that many stimuli can activate mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinases (PI3K) in human neutrophils, little is known concerning either the mechanisms or function of this activation. We have utilized a selective inhibitor of MAPK kinase (MEK), PD098059, and two inhibitors of PI3K, wortmannin and LY294002, to investigate the roles of these kinases in the regulation of neutrophil effector functions. Granulocyte/macrophage colony-stimulating factor, platelet-activating factor (PAF) and N-formylmethionyl-leucyl-phenylalanine are capable of activating both p44ERK1 and p42ERK2 MAPKs and phosphotyrosine-associated PI3K in human neutrophils. The activation of extracellular signal-related protein kinases (ERKs) is correlated with the activation of p21ras by both tyrosine kinase and G-protein-coupled receptors as measured by a novel assay for GTP loading. Wortmannin and LY294002 inhibit, to various degrees, superoxide generation, neutrophil migration and PAF release. Incubation with PD098059, however, inhibits only the PAF release stimulated by serum-treated zymosan. This demonstrates that, while neither MEK nor ERK kinases are involved in the activation of respiratory burst or neutrophil migration, inhibition of PAF release suggests a potential role in the activation of cytosolic phospholipase A2. PI3K isoforms, however, seem to have a much wider role in regulating neutrophil functioning.

This study shows that GOS/FOS supplementation induces a beneficial antibody profile. GOS/FOS reduces the total Ig response and modulates the immune response towards CMP, while leaving the response to vaccination intact. This suggests that oral GOS/FOS supplementation is a safe method to restrain the atopic march.

Orally applied nondigestible carbohydrates (NDC) have been associated with immune-modulating effects and other health benefits. The effects of prebiotic carbohydrates have recently received much attention, but other NDC have been reported to induce immune modulation as well. Many different effects have been shown on parameters of innate and specific immunity, mostly in animal experiments or in vitro. Data from clinical trials are limited, but promising studies have reported beneficial effects on mucosal and systemic immunity in humans. NDC are fermented to various degrees by the intestinal microbiota. Therefore, immune-modulatory properties have often been attributed to microbiota-dependent effects, especially in the case of prebiotic NDC. However, some NDC have been reported to bind to specific receptors on cells of the immune system, suggesting microbiota-independent, immune-modulatory effects play a role as well. This review aims to provide an overview of the published immune-modulatory effects in vitro and in vivo induced by NDC such as fructans, galactooligosaccharides, beta-glucans, pectins, and resistant starch. In addition, issues related to the underlying mechanisms are discussed: interaction between bacteria, their metabolites and the immune system, as well as direct effects of NDC via lectin receptors.

No abstract

No abstract

No abstract

Immunomodulatory effects of oligosaccharide preparations that resemble chemical and functional aspects of human milk oligosaccharides (HMOS) were studied for the development of new concepts in infant nutrition. A dose range of 1-5% (w/w) dietary pectin-derived acidic oligosaccharides (AOS) was tested in a murine influenza vaccination model. In addition, combinations of AOS and a 9:1 mixture of galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) were tested at a fixed total dietary dose of 2% (w/w). It was found that AOS significantly enhanced vaccine-specific delayed-type hypersensitivity (DTH) responses in a dose-dependent manner. This was accompanied by a reduction in T-helper2 (Th2) cytokine production by splenocytes in vitro. Overall, this indicates that the systemic immune response to the vaccine was Th1-skewed by the dietary intervention. Combinations of GOS/FOS and AOS were more effective in enhancing DTH responses than either of the oligosaccharides alone, suggesting interaction effects between these agents. Similar to effects in infants, supplementation of the murine diets with GOS/FOS and combinations of GOS/FOS and AOS for 6-wk enhanced the proportion of fecal bifidobacteria and lactobacilli, but AOS alone did not. In conclusion, these data indicate that GOS/FOS and AOS enhance systemic Th1-dependent immune responses in a murine vaccination model. As Th1-responses are weak in early life in humans, this might suggest that application of these oligosaccharides in infant formulas will be beneficial for the development of the infant's immune system.