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AIM: Much focus of immunotherapy for type 1 diabetes (T1D) has been devoted on selectively boosting regulatory T (Treg) cells using low dose IL-2 due to their constitutive expression of IL-2Rα, CD25. However, several clinical trials using a low dose of IL-2 only showed a limited improvement of metabolic control. It can therefore be hypothesized that further decreasing IL-2 dosage may increase the selective responsiveness of Treg cells. METHODS: We induced experimental T1D using multiple low dose streptozotocin (STZ) injections and treated the mice with an ultra-low dose IL-2 (uIL-2, approximately 7-fold lower than low dose). Immune response was studied using multicolor flow cytometry. RESULTS: We found that uIL-2 did not protect STZ mice from developing hyperglycemia. It did neither increase Treg cell proportions, nor did it correct the phenotypic shift of Treg cells seen in T1D. It only partially decreased the proportion of IFN-γ+ T cells. Likewise, uIL-2 also did not protect the dysfunction of regulatory B (Breg) cells. Strikingly, when administered in combination with an anti-inflammatory cytokine IL-35, uIL-2 abrogated IL-35's protective effect. Low dose IL-2, on the other hand, protected half of the STZ mice from developing hyperglycemia. No difference was found in the Treg and Breg response, and it only tended to decrease CD80 expression in macrophages and dendritic cells. CONCLUSION: In conclusion, further decreasing IL-2 dosage may not be a suitable approach for T1D therapy, and the limited success suggests that an alternative low dose IL-2 therapy strategy or other immunotherapies should be considered.
RESUMEN
BACKGROUND: Inadequate intraoperative mechanical ventilation (MV) can lead to ventilator-induced lung injury and increased risk for postoperative pulmonary complications (PPCs). Mechanical power (MP) was shown to be a valuable indicator for MV outcomes in critical care patients. The aim of this study is to assess the association between intraoperative MP in low-risk surgical patients undergoing general anesthesia and PPCs. METHODS: Two-hundred eighteen low-risk surgical patients undergoing general anesthesia for elective surgery were included in the study. Intraoperative mechanical ventilatory support parameters were collected for all patients. Postoperatively, patients were followed throughout their hospital stay and up to seven days post discharge for the occurrence of any PPCs. RESULTS: Out of 218 patients, 35% exhibited PPCs. The average body mass index, tidal volume per ideal body weight, peak inspiratory pressure, and MP were significantly higher in the patients with PPCs than in the patients without PPCs (30.3 ± 8.1 kg/m2 vs. 26.8 ± 4.9 kg.m2, p < 0.001; 9.1 ± 1.9 ml/kg vs. 8.6 ± 1.4 ml/kg, p = 0.02; 20 ± 4.9 cmH2O vs. 18 ± 3.7 cmH2O, p = 0.001; 12.9 ± 4.5 J/min vs. 11.1 ± 3.7 J/min, p = 0.002). A multivariable regression analysis revealed MP as the sole significant predictor for the risk of postoperative pulmonary complications [OR 1.1 (95% CI 1.0-1.2, p = 0.036]. CONCLUSIONS: High intraoperative mechanical power is a risk factor for developing postoperative pulmonary complications. Furthermore, intraoperative mechanical power is superior to other traditional mechanical ventilation variables in identifying surgical patients who are at risk for developing postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03551899; 24/02/2017.
