State of the art papers HLA-DR expression, cytokines and bioactive lipids in sepsis

Abstract

Sepsis accounts for more than 200,000 deaths annually in the USA alone. Both inflammatory and anti-inflammatory responses occur simultaneously in sepsis, the early phase dominated by the hyperinflammatory response and the late phase by immunosuppression. This late immunosuppression phase leads to loss of the delayed type hypersensitivity response, failure to clear the primary infection and development of secondary infections. Based on the available data, I hypothesize that failure to produce adequate amounts of inflammation resolving lipid mediators may be at the centre of both the hyperinflammatory response and late immunosuppression seen in sepsis. These proresolving lipids – lipoxins, resolvins and protectins – suppress exacerbated activation of leukocytes and macrophages, inhibit excess production of pro-inflammatory cytokines, initiate resolution of inappropriate inflammation, augment clearance of bacteria and other pathogens, and restore homeostasis. If true, this implies that administration of naturally occurring lipoxins, resolvins, protectins, maresins and nitrolipids by themselves or their more stable synthetic analogues such as 15-epi-16-(para-fluorophenoxy)-lipoxin A4-methyl ester, a synthetic analogue of 15-epi-lipoxin A4, and 15(R/S)-methyl-LXA4 may form a new approach in the prevention (in the high-risk subjects), management of sepsis and in resolving the imbalanced inflammatory process such that sepsis is ameliorated early. In addition, recent studies have suggested that nociceptin and cold inducible RNA binding protein (CIRBP) also have a role in the pathobiology of sepsis. It is suggested that both nociceptin and CIRBP inhibit the production of lipoxins, resolvins, protectins, maresins, and nitrolipids and thus play a role in sepsis and septic shock.

Combination of aspirin with essential fatty acids is superior to aspirin alone to prevent or ameliorate sepsis or ARDS

“…On the other hand, type 1 diabetic mice lacking 5-LOX or the receptor for LTB4 produced less IL-1β, survived polymicrobial sepsis, and had decreased bacterial counts [48]. These results [44–48] imply that under normal physiological condition there is a balance maintained between pro- and anti-inflammatory bioactive lipids (LTB4 vs LXA4/resolvins/protectins/maresins) to limit inflammation, regulate production of various cytokines, control bacterial proliferation and their ability to produce inflammation and ultimately control, prevent and help in the recovery from sepsis and ARDS as proposed previously [49, 50]. …”

“…In this context, it is worthwhile to measure plasma levels of lipid peroxides, various cytokines, PUFAs, LXA4, resolvins, protectins, maresins, LTB4 and correlate their concentrations to the severity and prognosis of sepsis and ARDS especially prior to embarking on the trial of aspirin with various PUFAs in order to know the dynamics of their changes in these patients as suggested previously [50]. Such a knowledge will gives us a better handle as to how much and when to administer aspirin, various PUFAs and possibly, LXA4, resolvins, protectins and maresins to those with sepsis and ARDS.…”

A Novel Highly Sensitive Method for Measuring Inflammatory Neural-Derived APC Activity in Glial Cell Lines, Mouse Brain and Human CSF

“…The inflammatory response consists of an early phase and a recovery phase. Inflammation resolving molecules is down-regulated in the early phase and up-regulated in the recovery phase [38]. APC has an anti-inflammatory effect, through tissue factor (TF), thrombin inhibition, and down-regulation of pro-inflammatory cytokines and chemokines [39].…”

Eicosanoids in carcinogenesis

“…The 15-LOX derived precursor molecule for LX biosynthesis, 15-S-hydroperoxyeicosatetraenoic acid (15-(S)-HpETE) is an active form of 15-HETE having 15(S)-configuration; it also functions as LTs antagonists [408]. Anti-inflammatory lipids such as LXA4 [408], RVs, PDs and MaRs [409], may function as a sentinel against a pathogenic stimulus and cytokinetriggered inflammatory overreaction. LXA4 together with LXB4 can inhibit LT-triggered polymorphonuclear neutrophils (PMN) [410].…”