IL-26 modulates T cell function in autoimmune hepatitis.

OBJECTIVES: Autoimmune hepatitis (AIH) is an aberrant autoimmune condition mediated by T cell abnormality, which may cause fulminant liver failure and persistent liver injury. This study aimed to disclose the histopathological and functional engagement of interleukin (IL)-26, a potent inflammation mediator, in AIH disease progression. METHODS: We conducted immunohistochemical staining on liver biopsy samples to evaluate intrahepatic expression of IL-26. Cellular sources of hepatic IL-26 were detected by confocal microscopy. Flow cytometry was employed to determine the immunological alterations of CD4+ and CD8+ T cells following in vitro IL-26 treatment on primary peripheral blood mononuclear cells from healthy controls. RESULTS: Statistically significant increase in IL-26 level was observed in AIH (n = 48) liver samples in comparison with patients having chronic hepatitis B (n = 25), nonalcoholic fatty liver disease (n = 18), and healthy donors for living donor liver transplantation (n = 10). The number of intrahepatic IL-26+ cells was positively correlated with histological and serological severity. An immunofluorescence staining indicated that liver-infiltrating CD4+ T cells, CD8+ T cells, and CD68+ macrophages orchestrated IL-26 secretion in AIH. Both CD4+ and CD8+ T cells demonstrated effective activation, lytic, and proinflammatory functions upon IL-26 stimulation. CONCLUSION: We observed elevated IL-26 in AIH liver which promoted T cell activation and cytotoxic capacity, indicating a therapeutic potential of IL-26 intervention in AIH.

Impact of obesity on outcomes in patients with acute respiratory syndrome.

OBJECTIVES: We assessed the relationship between obesity and all-cause mortality in patients with acute respiratory distress syndrome (ARDS). METHODS: In this retrospective cohort study, patient data were extracted from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care Database III. Body mass index (BMI) was grouped according to World Health Organization classifications: underweight, normal weight, overweight, obese. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality related to obesity. RESULTS: Participants included 185 women and 233 men, mean age 70.7 ± 44.1 years and mean BMI 28.7 ± 8.1 kg/m2. Compared with normal weight patients, obese patients tended to be younger (60.1 ± 13.7 years) and included more women (51.3% vs. 49.0%). In the unadjusted model, HRs (95% CIs) of 30-day mortality for underweight, overweight, and obesity were 1.57 (0.76, 3.27), 0.64 (0.39, 1.08), and 4.83 (2.25, 10.35), respectively, compared with those for normal weight. After adjustment, HRs (95% CIs) of 30-day mortality for underweight, overweight, and obesity were 1.82 (0.85, 3.90), 0.59 (0.29, 1.20), and 3.85 (1.73, 8.57), respectively, compared with the reference group; 90-day and 1-year all-cause mortalities showed similar trends. CONCLUSIONS: Obesity was associated with increased all-cause mortality in patients with ARDS.

Epinephrine Deteriorates Pulmonary Gas Exchange in a Rat Model of Bupivacaine-Induced Cardiotoxicity: A Threshold Dose of Epinephrine.

BACKGROUND AND OBJECTIVE: The study goal was to compare the effect of epinephrine in different doses on pulmonary gas exchange in a rat model of bupivacaine-induced cardiac depression. METHODS: Twenty-four adult male Sprague-Dawley rats were divided into 4 groups (n = 6), and each group received a bupivacaine infusion (2.5 mg/kg per minute, 6 minutes) via the left femoral vein to induce cardiac depression. At the end of the bupivacaine infusion, each group was immediately given either isotonic sodium chloride solution (normal saline; NS group), 5-µg/kg epinephrine (Epi5 group), 10-µg/kg epinephrine (Epi10 group), or 20 µg/kg epinephrine (Epi20 group). Left atrial pressures were monitored for 20 minutes after epinephrine was administered (as was the NS group). Arterial blood gas analyses were performed before bupivacaine infusion and at the end of the 20-minute monitoring period. RESULTS: The Epi10 and Epi20 groups had lower pH (P = 0.02 and P < 0.001, respectively) and PaO2 (P = 0.049 and P < 0.001, respectively), and a higher PaCO2 (P < 0.001 and P < 0.001, respectively) compared with the NS group. There were no statistical differences between the Epi5 and NS groups in pH, PaCO2, or PaO2. Left atrial systolic pressure was higher in the Epi10 group (P = 0.002) and the Epi20 group (P < 0.001) within 2 minutes of epinephrine administration. There was no statistical difference between the Epi5 and NS groups in left atrial systolic pressure. CONCLUSION: A single injection of 10 µg/kg epinephrine or greater was associated with deterioration of pulmonary gas exchange in our rat model of bupivacaine induced cardiac depression.