BackgroundInfluenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established.MethodsMice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi.ResultsSupra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an “M1-like” to a more “M2-like” activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ).ConclusionsOur data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic “M1-like” macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.Electronic supplementary materialThe online version of this article (10.1186/s12931-017-0708-5) contains supplementary material, which is available to authorized users.

To explore the relationship between neutrophil-to-lymphocyte ratio (NLR) and diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus.A total of 557 newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients were recruited, including 397 T2DM patients without complication (DM group) as well as 160 T2DM patients complicated with DPN (DPN group). Student t test, Mann–Whitney U test, or χ2 test was applied to the data of the 2 groups, including the levels of neutrophils and lymphocytes as well as the NLR values of peripheral blood and other biochemistry indexes; Pearson correlation analysis was used to calculate the correlation of NLR and detected factors; risk factors of DPN were estimated via logistic regression analysis and multivariate analysis.The values of triglyceride (TG), neutrophils, fasting insulin, urinary albumin, and 2 hour postglucose in DPN group were significantly higher than those of the DM group, whereas the number of lymphocytes of DPN group was considerably lower than that of the DM group (P < .05 respectively); NLR values were remarkably higher in DPN group compared with those of DM group (2.58 ± 0.50 vs 2.18 ± 0.61, P < .001); logistic regression analysis showed that NLR (P = .002, OR = 4.960, 95% CI = 1.843–13.349) was a risk factor of DPN. Multivariate logistic regression analysis showed that DPN was independently related to NLR (P = .002, OR = 4.960, 95% CI = 1.843–13.349). The ROC curve analysis confirmed that the optimal cut-off point, specificity, and sensitivity in diagnosing DPN by NLR were 2.13%, 48.1%, and 81.3% respectively.Our results showed that NLR is significantly correlated with DPN, which suggested that NLR may be an independent risk factor of DPN.

The general methods which are powerful for the necessity of bounded commutators are given. As applications, some necessary conditions for bounded commutators are first obtained in certain endpoint cases, and several new characterizations of BM O spaces, Lipschitz spaces and their weighted versions via boundedness of commutators in various function spaces are deduced.2010 Mathematics Subject Classification. 42B20; 42B25.