Effects of Ketamine and Propofol on the Ratio of Interleukin-6 to Interleukin-10 during Endotoxemia in Rats

Our previous study reported that the change in the ratio of interleukin (IL)-6 to IL-10 influences the severity of sepsis in patients with systemic inflammatory response syndrome. We evaluated the change in the ratio of IL-6 to IL-10 after administration of ketamine or propofol in endotoxin-exposed rats in order to evaluate the relationship of pro-inflammatory and anti-inflammatory cytokines following ketamine or propofol administration during endotoxemia. We randomly assigned 40 rats to one of four equal groups: endotoxin alone, receiving Escherichia coli endotoxin (15 mg-/kg, i.v.); saline control; ketamine (10 mg·kg−1·h−1, i.v.) before and during exposure to endotoxin; and propofol (10 mg·kg−1·h−1, i.v.) before and during exposure to endotoxin. We measured the plasma concentrations of tumor necrosis factor (TNF)-α, IL-6, and IL-10 and calculated the ratio of IL-6 to IL-10 in each group. The current study showed that ketamine and propofol administration attenuated the increase in TNF-α, IL-6, and IL-10, and ketamine attenuated the increase in the ratio of IL-6 to IL-10, but propofol increased this ratio in rats receiving a single intravenous bolus of endotoxin. While the mechanisms responsible for the inhibitory effects require further investigation, our results suggest that proper use of ketamine as an anesthetic agent may offer certain advantages in the management of patients with endotoxemia

Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

BACKGROUND: Transfusion of packed red blood cells (PRBCs) saves lives in the neonatal critical care setting and is one of the most common interventions in the preterm infant. The number and volume of PRBC transfusions are associated with several major neonatal morbidities, although a direct causal link between transfusion and major neonatal morbidity is still to be proven. Transfusion-related immunomodulation (TRIM) may underlie these adverse outcomes, yet it has received little attention in the high-risk preterm infant. METHODS: One transfusion event was studied in infants ≤28 wk gestation between 2 and 6 wk postnatal age (n = 28). Plasma inflammatory cytokines and markers of endothelial activation were measured in the infants before and 2–4 h after transfusion, as well as in the donor pack. RESULTS: Median (range) age at transfusion was 18 (14–39) days with the pretransfusion hemoglobin level at 9.8 (7.4–10.2) g/dl. Interleukin (IL)-1β (P = 0.01), IL-8 (P = <0.001), tumor necrosis factor-α (P = 0.008), and monocyte chemoattractant protein (P = 0.01) were increased after transfusion. A similar elevation in markers of endothelial activation was seen after transfusion with increased plasma macrophage inhibitory factor (P = 0.005) and soluble intracellular adhesion molecule-1 (P = <0.001). CONCLUSION: Production of inflammatory cytokines and immunoactivation of the endothelium observed after the transfusion of PRBCs in the preterm infant may be a manifestation of TRIM. The implications of this emerging phenomenon within the preterm neonatal population warrant further investigation.Amy K. Keir, Andrew J. McPhee, Chad C. Andersen and Michael J. Star

Gene networks specific for innate immunity define post-traumatic stress disorder

The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD

Transfusion-related acute lung injury (TRALI): Current concepts and misconceptions

Transfusion-related acute lung injury (TRALI) is the most common cause of serious morbidity and mortality due to hemotherapy. Although the pathogenesis has been related to the infusion of donor antibodies into the recipient, antibody negative TRALI has been reported. Changes in transfusion practices, especially the use of male-only plasma, have decreased the number of antibody-mediated cases and deaths; however, TRALI still occurs. The neutrophil appears to be the effector cell in TRALI and the pathophysiology is centered on neutrophil-mediated endothelial cell cytotoxicity resulting in capillary leak and ALI. This review will detail the pathophysiology of TRALI including recent pre-clinical data, provide insight into newer areas of research, and critically assess current practices to decrease it prevalence and to make transfusion safer