Proinflammatory versus anti-inflammatory response in sepsis patients: looking at the cytokines

Abstract

Introduction: During the course of systemic inflammation, most of the immune cell types get activated to a certain degree as part of, or contributing to, the cascade of physiopathological events. Whether for some cells, classically phagocytes of the innate immune system, it is clear that direct sensing of pathogen-associated molecular patterns leads to activation initiating systemic inflammation, the picture is not so clear for natural killer (NK) cells. While NK cells have been shown to express toll-like receptors (TLR), the role of these receptors on NKs during systemic inflammation has not been directly addressed. Methods: To directly assess the role of TLR expression on NK cells we used an adoptive transfer model in which NKs purified from the spleens of WT, TLR4KO and TLR2/4DKO mice were transferred intravenously to RAG2 -/-γc -/-(devoid of T, B and NK cells). Five days after reconstitution the mice were challenged intraperitoneally with conventional or TLR-grade lipopolysaccharide (LPS). Immune cell activation and production of IFNγ by NK cells was determined after 6 hours by FACS analysis. Results: We observed no differences in reconstitution of the recipient mice with NK cells from different backgrounds suggesting no difference in trafficking and survival of the transferred cells. At 6 hours after LPS challenge, WT, TLR4KO or TLR2/4DKO NK cells recovered from the spleen and lungs of RAG2 -/-γc -/-mice showed comparable levels of CD69 activation marker expression. Intracellular labeling for IFNγ in NK cells also revealed no significant differences. Conclusion: Whether there is a role for direct TLR signaling on NK cells remains the objective of further investigations; however, our data show that in the course of a systemic inflammatory process, like endotoxinemia, the expression of TLR2 and TLR4 by NK cells makes no difference in terms of their activation and secretion of IFNγ P2 Role of 6-hour, 12-hour, and 24-hour lactate clearance in mortality of severe sepsis and septic shock patients. Introduction: Lactate is one of biomarkers used for risk stratification, resuscitation target, and death prediction in sepsis [1,2]. Interpretation of lactate clearance was proven more superior than single measurement to evaluate resuscitation adequacy and to determine prognosis [3,4]. This study aimed to find out whether mean differences of 6-hour, 12-hour, and 24-hour lactate clearance were observed between nonsurvivors and survivors of acute phase mortality in severe sepsis and septic shock patients. Methods: The study design was prospective cohort. Subjects were collected by consecutive sampling from the emergency department, hospital ward, and ICU at Cipto Mangunkusumo Hospital, Jakarta. Lactate levels were measured at 6, 12, and 24 hours, and subjects were subsequently followed to evaluate 3-day mortality. To determine their association with mortality, we used mean difference analysis of those three lactate clearance periods between nonsurvivors and survivors. In addition, to determine the cutoff value, we used re...

MALAT1 modulates miR-146’s protection of microvascular endothelial cells against LPS-induced NF-κB activation and inflammatory injury

“…It is widely accepted that inflammatory cytokines such as TNF-α and IL-6, and related signalling pathways such as NF-κB signalling, play an important role in the pathogenesis of sepsis. 3–5 However, deeper insights into the development of sepsis, especially the underlying molecular mechanisms, are still unclear. The studies focusing on the underlying mechanisms of sepsis will certainly bring new hope for the treatment and prevention of sepsis.…”

Effectiveness of hemoperfusion (HP) in hemodialysis (HD) patients with Covid-19 infection

“…We all are familiar with the so called "cytokine storm syndrome" (CSS). In many life-threatening conditions such as sepsis, if homeostasis has not been restored, an uncontrolled pro-inflammatory response along with an unbalanced anti-inflammatory feedback causes production of excess inflammatory mediators, particularly cytokines [11] . Cytokines are a family of immunoregulatory molecules that play roles in the regulation of pro and anti-inflammatory responses.…”

Research on the effect of cytokine concentration on the immune level and survival conditions of elderly patients with sepsis

“…IL-6 can directly activate the inflammatory cells and vascular endothelial cells, and is also toxic to them; besides, it can intensify the toxicity and inflammatory responses, which can harm the tissues and cells ( 13 ). As a key member in pro-inflammatory transmitters, IL-6 can induce the differentiation of lymphocyte B, activate the lymphocyte T, and act on the tissues and cells through autocrine or paracrine, thus promoting the hyperplasia of extracellular matrix, promoting cell growth and being involved in the inflammatory responses ( 14 ).…”