The expression of CD86 in CD3+CD56+ NKT cells is associated with the occurrence and prognosis of sepsis-associated encephalopathy in sepsis patients: a prospective observational cohort study.

The role of CD3+CD56+ natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3+CD56+ NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan-Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ2 = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3+CD56+ NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis.

Hypercapnia promotes microglial pyroptosis via inhibiting mitophagy in hypoxemic adult rats.

BACKGROUND: Hypoxemia is a typical symptom of acute respiratory distress syndrome. To avoid pulmonary morbidity, low tidal volume ventilation is often applied. The ventilation strategy will certainly cause hypercapnia. This study aimed to explore whether hypercapnia would promote microglial pyroptosis via inhibiting mitophagy in adult rats with hypoxemia. METHODS: The cerebral oxygen extraction ratio (CERO2 ) and partial pressure of brain tissue oxygen (PbtO2 ) in a rat model of hypercapnia/hypoxemia were assessed. The reactive oxygen species (ROS) production and the expression of LC3-II/I, p62, caspase-1, gasdermin D-N domains (GSDMD-N), IL-1ß, and IL-18 in microglial cells were detected. RESULTS: Hypercapnia decreased the PbtO2 levels of the hypoxic rats, which was further evidenced by the increased levels of CERO2 . Expression levels of LC3-II were reduced, while p62 expression was increased by hypercapnia in hypoxic microglia. Hypercapnia increased the production of ROS and the expression of caspase-1, GSDMD-N, IL-1ß, and IL-18 in hypoxia-activated microglia. Scavenging ROS inhibited microglial pyroptosis and expression of IL-1ß and IL-18. CONCLUSIONS: These results suggest that hypercapnia-induced mitophagy inhibition may promote pyroptosis and enhance IL-1ß and IL-18 release in hypoxia-activated microglia.