Lipoproteins in inflammation and sepsis. II. Clinical aspects

Abstract

Nutritional lipids supplied during critical illness have been shown to modulate the host response to inflammation. In particular, inclusion of omega-3 fatty acids seems to have beneficial effects on cellular immunity and helps to maintain the balance between pro- and anti-inflammatory cytokines thereby preventing hyperinflammatory complications. In addition to improvements in the profile of lipid mediators generated, omega-3 fatty acids act as activating ligands of peroxisome proliferator-activated receptors and directly inhibit nuclear factor kappaB mediated proinflammatory signaling. We present an overview on the alterations in the metabolism of serum lipoproteins during sepsis and present data from clinical studies and discuss the significance of nutritional lipids and their role in immunomodulation with special emphasis on omega-3 fatty acids.

HDL in Infectious Diseases and Sepsis

“…During infection, significant changes in the lipid metabolism are observed. At first, plasma levels of lipid and lipoproteins may change: triglyceride (TG) and VLDL cholesterol levels increase due to several mechanisms, including reduction of TG hydrolysis, LPS-and pro-inflammatory cytokines-induced de novo free fatty acid production, and TG synthesis in the liver and reduction of lipoprotein lipase activity thus resulting in reduced VLDL clearance and increased TG levels (Wendel et al 2007). In addition, the increase in free fatty acids induces insulin resistance, thus contributing to increased glucose levels during systemic inflammation.…”

“…Also the lipid composition of HDL is altered during the acute-phase response (Khovidhunkit et al 2004). Endotoxemia induces the increase of some enzymes involved in HDL remodeling, including endothelial lipase (Badellino et al 2008) and secretory phospholipase A2 (de la Llera et al 2012), and the decrease of other, such as CETP and LCAT (de la Llera et al 2012;Wendel et al 2007). Altogether these changes result in the loss of functional properties of HDL (Banka et al 1995;de la Llera et al 2012;McGillicuddy et al 2009).…”

“…Low HDL-C levels inversely correlate with the severity of septic disease and associate with an exaggerated systemic inflammatory response (Wendel et al 2007), although it is difficult to establish whether changes in plasma lipoproteins simply reflect the severity of disease or they can directly modify the host response to inflammation. Also in healthy subjects low HDL levels are associated with increased inflammatory response on endotoxin challenge compared to subjects with normal or high HDL levels (Birjmohun et al 2007), without differences in the HDL proteome (Levels et al 2011).…”

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction

“…A similar cardioprotective and antiapoptotic action of HDL have been shown through the activation of Stat3 mediated by sphingosine 1 phosphate (S1P), one of their common component [108]. The recombinant HDL(rHDL) or HDL mimetics, currently under clinical trial, are provided with the same actions attributed to the HDL [109,110]. The level of total, HDL-and LDL-cholesterol is decreased in septic and critically ill patients, as well as in experimental animals infused with LPS and proinflammatory cytokines and the decrease is negatively related to IL6 and TNFa concentrations [111]; HDL reduction is also related to mortality and severity of the disease [105,106].…”

Haemophagocytic lymphohistiocytosis in Adult- A Case Report and Literature Review

“…It is important to consider the fact that none of these eight criteria are specific for HLH diagnosis and might be found in sepsis, SIRS and MODS. [74][75][76] For example the etiology of hypertriglyceridemia in these states can be multifactorial such as insulin resistance 77,78 and inhibition of lipoprotein lipase activity. 79,80 High level of serum ferritin has also been associated with inflammatory states and is frequently seen in toxic patients due to the up regulation of hemoxygenase-1 (heat shock protein).…”