T lymphocyte alterations are central to sepsis pathophysiology, whereas related mechanisms remain poorly understood. We hypothesized that metabolic alterations could play a role in sepsis-induced T lymphocyte dysfunction. Samples from septic shock patients were obtained at day 3 and compared with those from healthy donors. T cell metabolic status was evaluated in the basal condition and after T cell stimulation. We observed that basal metabolic content measured in lymphocytes by nuclear magnetic resonance spectroscopy was altered in septic patients. Basal ATP concentration, oxidative phosphorylation (OXPHOS), and glycolysis pathways in T cells were decreased as well. After stimulation, T lymphocytes from patients failed to induce glycolysis, OXPHOS, ATP production, GLUT1 expression, glucose entry, and proliferation to similar levels as controls. This was associated with significantly altered mTOR, but not Akt or HIF-1α, activation and only minor AMPKα phosphorylation dysfunction. IL-7 treatment improved mTOR activation, GLUT1 expression, and glucose entry in septic patients' T lymphocytes, leading to their enhanced proliferation. mTOR activation was central to this process, because rapamycin systematically inhibited the beneficial effect of recombinant human IL-7. We demonstrate the central role of immunometabolism and, in particular, mTOR alterations in the pathophysiology of sepsis-induced T cell alterations. Our results support the rationale for targeting metabolism in sepsis with recombinant human IL-7 as a treatment option.

Ultrasound measurement of the antral cross-sectional area allows a quantitative estimate of gastric contents in non-pregnant adults, but this relationship may be affected by compression of the stomach exerted by the gravid uterus during pregnancy. This study aimed to assess differences in quantitative (Perlas score) and qualitative (antral cross-sectional area) ultrasound assessments of the gastric antrum performed immediately before and after caesarean section. Forty-three women having elective caesarean section performed under spinal anaesthesia were studied in the semirecumbent and semirecumbent-right lateral positions. Thirty-nine women showed no change in stomach contents using the Perlas score between the two measurement periods; four women showed a change, but by one grade only. The median (IQR [range]) antral cross-sectional area was 323 (243-495 [103-908]) mm before, and 237 (165-377 [112-762]) mm after, caesarean section in the semirecumbent position (p = 0.001); the comparable values in the semirecumbent-right lateral position were 418 (310-640 [161-1238]) mm and 362 (280-491 [137-1231]) mm (p = 0.09). The distance between the skin and the antrum, and the aorta and the antrum, decreased significantly in both positions after surgery. We suggest that our results indicate that stomach contents remain largely unchanged in women having elective caesarean section, but antral cross-sectional area decreases, especially in the semirecumbent position, related to a change in the position of the stomach within the abdomen. This implies that the relationship of antral cross-sectional area to volume of stomach contents, which has been determined for non-pregnant subjects, may not apply in term pregnant women.

Septic patients develop immune dysfunctions, the intensities and durations of which are associated with deleterious outcomes. LILRB2 (leukocyte immunoglobulin-like receptors subfamily B, member 2), an inhibitory member of the LILR family of receptors, is known for its immunoregulatory properties. In a microarray study, we identified LILRB2 as an upregulated gene in septic shock patients. On monocytes primed with LPS ex vivo, LILRB2 mRNA and protein expressions were dose-dependently downregulated and subsequently highly upregulated versus non-stimulated cells. This is concordant with clinical data, since both LILRB2 mRNA and protein expressions were significantly increased in septic shock patients at day 3. In a cohort of more than 700 patients, only after septic shock were LILRB2 mRNA levels increased compared with non-infected or less severely infected patients. This was preceded by a phase of downregulated mRNA expression during the first hours after septic shock. Interestingly, the intensity of this decrease was associated with increased risk of death after septic shock. LILRB2 protein and mRNA expressions are deregulated on monocytes after septic shock and this can be reproduced ex vivo after LPS challenge. Considering LILRB2 inhibitory properties, we can hypothesize that LILRB2 may participate in the altered immune response after septic shock.