In a recent study, we reported that interleukin (IL)-4 had a protective role against acetaminophen (APAP)-induced liver injury (AILI), although the mechanism of protection was unclear. Here, we carried out more detailed investigations and have shown that one way IL-4 may control the severity of AILI is by regulating glutathione (GSH) synthesis. In the present studies, the protective role of IL-4 in AILI was established definitively by showing that C57BL/6J mice made deficient in IL-4 genetically (IL-4−/−) or by depletion with an antibody, were more susceptible to AILI than mice not depleted of IL-4. The increased susceptibility of IL-4−/− mice was not due to elevated levels of hepatic APAP-protein adducts, but was associated with a prolonged reduction in hepatic GSH that was attributed to decreased gene expression of γ-glutamylcysteine ligase (γ-GCL). Moreover, administration of recombinant IL-4 to IL-4−/− mice post-acetaminophen treatment diminished the severity of liver injury and increased γ-GCL and GSH levels. We also report that the prolonged reduction of GSH in APAP-treated IL-4−/− mice appeared to contribute towards increased liver injury by causing a sustained activation of c-Jun-N-terminal kinase (JNK), since levels of phosphorylated JNK remained significantly higher in the IL-4−/− mice up to 24 hours after APAP treatment Conclusion Overall these results show for the first time that IL-4 has a role in regulating the synthesis of GSH in the liver under conditions of cellular stress. This mechanism appears to be responsible at least in part for the protective role of IL-4 against AILI in mice and may have a similar role not only in AILI in humans, but also in pathologies of the liver caused by other drugs and etiologies.

Our study is the first diverse analysis of unplanned postoperative ICU admissions in the literature across multiple specialties and practice models. We found an association of advanced age, higher ASA PS class, and duration of procedure with unplanned ICU admission after surgery. Surgical specialties and procedures with the most unplanned ICU admissions could be areas for quality improvement and clinical pathways in the future.

Pulmonary complications post-hematopoietic stem cell transplantation (HSCT) such as diffuse alveolar hemorrhage (DAH) can occur in 2%-14% of HSCT patients with a mortality greater than 80%. [1][2][3][4] It is described as a syndrome of acute respiratory failure characterized by diffuse bilateral infiltrates and progressive hemorrhage and manifests as bleeding in the alveolar space due to injury to the alveolar-capillary basement membrane. 4,5 Clinical symptoms include cough, hypoxemia, and fever. [1][2][3][4] Imaging findings, either by x-ray or