Immunonutrition

Purpose of review: To outline recent findings on the efficacy of immunonutrients in patients undergoing inflammatory stress due to surgery, infection and cancer.Recent findings: Enteral nutrition is more efficacious and poses lower risks than parenteral nutrition. It reduces infection rates and shortens ICU and hospital length of stay of critically ill patients. Beneficial effects of immunonutrition are most apparent in malnourished patients. Perioperative enteral nutrition is more effective than postoperative nutrition. In Crohn disease similar remission rates are achieved with enteral nutrition as with steroids. Glutamine, omega-3 fatty acids and antioxidants exert beneficial influences in diverse patient populations. L-arginine is an important immunonutrient having both beneficial and adverse effects. The former effect occurs in necrotizing enterocolitis; the latter influence is seen in septic patients. The gut plays a major role in whole body amino acid metabolism, particularly arginine homeostasis. Arginase and nitric oxide synthetase compete for arginine within immune cells and play a pivotal role in clinical outcome during infection. In cancer a range of antioxidants are able to ameliorate immunosuppression. Intravenous lipids may be deleterious due to the pro-inflammatory effects of omega-6 fatty acids. Omega-3 fatty acids are anti-inflammatory and combined with medium chain triglyceride (MCT) and olive oil may provide a more efficacious form of intravenous lipid.Summary: Immunonutrition is effective in improving outcome in a wide range of patients when applied enterally, particularly in malnourished individuals. Parenteral immunonutrition carries a higher risk but can be efficacious in selected patient groups for whom enteral nutrition is problematic

Omega-3 fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment

Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-?, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA), arachidonic acid, into the eicosanoid prostaglandin-D2 (PGD2) by cyclooxygenase (COX) enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA), was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD3. This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD2 receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD2 signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not only revealed an unsuspected level of regulation in the migration of inflammatory leukocytes, it also contributes to our understanding of the interactions of this bioactive lipid with the inflammatory system. Moreover, it indicates the potential for novel therapeutics that target the inflammatory system with greater affinity and/or specificity than supplementing the diet with n-3-PUFA

Long-chain n-3 fatty acid supplementation in men increases resistance to activated protein C

It has recently and controversially been demonstrated that fish oil supplementation may not be beneficial for everyone, but to date there have been no biological explanations. We suggest that resistance to the anticoagulant, activated protein C (APC), be considered as a potential mechanism, because it has been demonstrated that the type of fatty acids on phospholipids modulates function of the APC pathway. The APC ratio in plasma was decreased by 7% after fish oil supplementation in healthy men (P<.005; n=35). The decrease in APC ratio equates to an increase in APC resistance. Fish oil lowered the APC ratio by (1) increasing low-density lipoprotein (LDL) cholesterol (P<.01) and apolipoprotein B (P<.05) and (2) increasing platelet microparticles (P<.05). In vitro, purified LDL decreased the APC ratio and increased microparticle formation. These changes affecting the anticoagulant APC could contribute toward a prothrombotic state, potentially explaining the recent observation that fish oil supplementation may not always be of benefit. These findings will need to be repeated in different disease states

Managing hypercholesterolemia and its correlation with carotid plaque morphology in patients undergoing crotid endarterectomy

Purpose: hypercholesterolemia is a critical problem in patients with carotid atherosclerosis. The adequacy of attention to lipid risk factors in patients with carotid stenosis awaiting carotid endarterectomy (CEA) has rarely been studied. We also assessed patient awareness of hypercholesterolemia and carotid plaque morphology.Methods: a prospective study was conducted of 141 consecutive patients admitted electively for CEA. Each patient’s medical history was taken. Plasma cholesterol concentrations were determined. Plaque histology was scored according to American Heart Association criteria and their modification.Results: of patients who were aware of their hypercholesterolemia and who were receiving treatment, 28.6% had total cholesterol levels ?5 mmol/L. Among those patients who had been told that they had no problem with hypercholesterolemia, 32.5% had plasma cholesterol concentrations ?5 mmol/L. Among those patients who had never had their plasma cholesterol measured, 48.4% had total cholesterol levels ?5 mmol/L. Patients in this last group tended to have more severe types of plaque pathology than those in other groups (12.9% plaque rupture).Conclusions: hypercholesterolemia does not seem to be well managed in patients awaiting CEA