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Background/Objective: The aim of study is to assess the efficacy of each ventilator weaning method for ventilated patients in intensive care units (ICUs).Methods: A systematic search was conducted using PubMed, Embase, and China National Knowledge Infrastructure to identify randomized control studies on ventilated patients regarding extubation associated outcomes (weaning success or failure, proportion requiring re-intubation, or mortality) from inception until April 01, 2020. Commonly used ventilation modes involved pressure support ventilation, synchronized intermittent mandatory ventilation, automatic tube compensation, continuous positive airway pressure, adaptive support ventilation, neurally adjusted ventilatory assist, proportional assisted ventilation, and SmartCare. Pooled estimates regarding extubation associated outcomes were calculated using network meta-analysis.Results: Thirty-nine randomized controlled trials including 5,953 patients met inclusion criteria. SmartCare and proportional assist ventilation were found to be effective methods in increasing weaning success (odds ratio, 2.72, 95% confidence interval (CI), 1.33–5.58, P-score: 0.84; odds ratio, 2.56, 95% CI, 1.60–4.11, P-score: 0.83; respectively). Besides, proportional assist ventilation had superior in reducing proportion requiring re-intubation rate (odds ratio, 0.48, 95% CI, 0.25–0.92, P-score: 0.89) and mortality (odds ratio, 0.48, 95% CI, 0.26–0.92, P-score: 0.91) than others.Conclusion: In general consideration, our study provided evidence that weaning with proportional assist ventilation has a high probability of being the most effective ventilation mode for patients with mechanical ventilation regarding a higher rate of weaning success, a lower proportion requiring reintubation, and a lower mortality rate than other ventilation modes.

Protease-activated receptor (PAR)-1 is a thrombin-activated receptor that plays an essential role in ischemia/reperfusion (IR)-induced acute inflammation. PAR-1 antagonists have been shown to alleviate injuries in various IR models. However, the effect of PAR-1 antagonists on IR-induced acute lung injury (ALI) has not yet been elucidated. This study aimed to investigate whether PAR-1 inhibition could attenuate lung IR injury. Lung IR was induced in an isolated perfused rat lung model. Male rats were treated with the specific PAR-1 antagonist SCH530348 (vorapaxar) or vehicle, followed by ischemia for 40 min and reperfusion for 60 min. To examine the role of PAR-1 and the mechanism of SCH530348 in lung IR injury, western blotting and immunohistochemical analysis of lung tissue were performed. In vitro, mouse lung epithelial cells (MLE-12) were treated with SCH530348 or vehicle and subjected to hypoxia-reoxygenation (HR). We found that SCH530348 decreased lung edema and neutrophil infiltration, attenuated thrombin production, reduced inflammatory factors, including cytokine-induced neutrophil chemoattractant-1, interleukin-6 and tumor necrosis factor-α, mitigated lung cell apoptosis, and downregulated the phosphoinositide 3-kinase (PI3K), nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in IR-injured lungs. In addition, SCH530348 prevented HR-induced NF-κB activation and inflammatory chemokine production in MLE12 cells. Our results demonstrate that SCH530348 exerts protective effects by blocking PAR-1 expression and modulating the downstream PI3K, NF-κB and MAPK pathways. These findings indicate that the PAR-1 antagonist protects against IR-induced ALI and is a potential therapeutic candidate for lung protection following IR injury.

BackgroundVentilator-induced lung injury (VILI) is characterized by vascular barrier dysfunction and suppression of alveolar fluid clearance (AFC). Obesity itself leads to chronic inflammation, which may initiate an injurious cascade to the lungs and simultaneously induce a protective feedback. In this study, we investigated the protective mechanism of obesity on VILI in a mouse model.MethodsThe VILI model was set up via 6-h mechanical ventilation with a high tidal volume. Parameters including lung injury score, STAT3/NFκB pathway, and AFC were assessed. Mice with diet-induced obesity were obtained by allowing free access to a high-fat diet since the age of 3 weeks. After a 9-week diet intervention, these mice were sacrificed at the age of 12 weeks. The manipulation of SOCS3 protein was achieved by siRNA knockdown and pharmaceutical stimulation using hesperetin. WNK4 knockin and knockout obese mice were used to clarify the pathway of AFC modulation.ResultsObesity itself attenuated VILI. Knockdown of SOCS3 in obese mice offset the protection against VILI afforded by obesity. Hesperetin stimulated SOCS3 upregulation in nonobese mice and provided protection against VILI. In obese mice, the WNK4 axis was upregulated at the baseline, but was significantly attenuated after VILI compared with nonobese mice. At the baseline, the manipulation of SOCS3 by siRNA and hesperetin also led to the corresponding alteration of WNK4, albeit to a lesser extent. After VILI, WNK4 expression correlated with STAT3/NFκB activation, regardless of SOCS3 status. Obese mice carrying WNK4 knockout had VILI with a severity similar to that of wild-type obese mice. The severity of VILI in WNK4-knockin obese mice was counteracted by obesity, similar to that of wild-type nonobese mice only.ConclusionsObesity protects lungs from VILI by upregulating SOCS3, thus suppressing the STAT3/NFκB inflammatory pathway and enhancing WNK4-related AFC. However, WNK4 activation is mainly from direct NFκB downstreaming, and less from SOCS3 upregulation. Moreover, JAK2–STAT3/NFκB signaling predominates the pathogenesis of VILI. Nevertheless, the interaction between SOCS3 and WNK4 in modulating VILI in obesity warrants further investigation.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by recurrent exacerbations. Macrophages play a critical role in immune response and tissue repair in COPD. Airway macrophages (AM) are exposed to environmental exposures which are retained in the cytoplasmic material. Both biomass and particulate matter have been linked to higher AM black carbon. It is unknown if AM black carbon is associated with COPD morbidity and macrophage phenotype. Methods: Former smokers with COPD were enrolled and sputum induction was performed to obtain airway macrophages. Macrophages underwent black carbon quantification and flow cytometry phenotyping. Health information was obtained the same day as sputum induction and prospective exacerbations were assessed by monthly telephone calls. Results: We studied 30 former smokers with COPD who had a mean age of 67 years and mean forced expiratory volume in 1 second (FEV(1))% predicted of 60.8%. Higher AM black carbon content was associated with increased total exacerbations and severe exacerbations and reduced CD80 expression. Conclusion: AM black carbon association with respiratory morbidity is largely unexplored and this is the first study to identify association with prospective exacerbations. Macrophages expressed reduced CD80, a surface marker providing costimulatory signals required for development of antigen-specific immune responses. Our findings suggest that reduced CD80 expression is the pathophysiologic mechanism for the association of AM black carbon content and increased exacerbations. Therefore, beyond solely serving as a marker for increased exposures, AM black carbon content may be a predictor of future exacerbations given a macrophage less equipped to respond to an acute infectious exposure.

We report on a 70-year-old man with fever, leukopenia, thrombocytopenia, vomiting, malaise, dyspnea, and consciousness disturbance who was infected with severe fever with thrombocytopenia syndrome virus in northern Taiwan, 2019. This autochthonous case was confirmed by reverse transcription PCR, virus isolation, and genomic sequencing.

Chih-Jen Yang,1 Wen-I Liao,1 Zun-Cheng Tang,2 Jen-Chun Wang,1 Chien-Hsing Lee,3 Wei-Chou Chang,4 Chin-Wang Hsu,5,6 Shih-En Tang,7 Shih-Hung Tsai1 1Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, 2Department of Biological Imaging and Radiological Science, National Yang-Ming University, 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 4Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, 5Department of Emergency Medicine, School of Medicine, College of Medicine, 6Department of Emergency and Critical Medicine, Wan Fang Hospital, Taipei Medical University, 7Division of Pulmonary and Critical Care, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Abstract: Acute hyperglycemia is a common finding in patients presenting to emergency departments (EDs) with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Several studies have argued against the association between hyperglycemia at admission and adverse outcomes in patients with diabetes and an acute illness. Recent studies have shown that glucose-related variables (eg, glycemic gaps and stress hyperglycemia ratios) that are adjusted for glycated hemoglobin levels can indicate the severity of a variety of diseases. The objective of this study was to assess whether these hemoglobin A1c (HbA1c)-based adjusted average glycemic variables were associated with unfavorable outcomes in patients admitted to a hospital with AECOPD. We found that 1) pulmonary infection is a major risk factor for AECOPD; 2) a higher glycemic gap and modified stress hyperglycemia ratio were associated with the development of acute respiratory failure (ARF) in patients with diabetes admitted to an ED because of AECOPD; and 3) the glycemic gap and modified stress hyperglycemia ratio had superior discriminative power over acute hyperglycemia and HbA1c for predicting the development of ARF, although the HbA1c-adjusted glycemic variables alone were not independent risk factors for ARF. Keywords: chronic obstructive pulmonary disease, diabetes mellitus, acute respiratory failure, glycated hemoglobin, hyperglycemia, glycemic gap, stress hyperglycemia ratio

Current treatments for ischemia-reperfusion (IR)-induced acute lung injury are limited. Mesenchymal stem cell-conditioned medium (CM) has been reported to attenuate lung injury. Neural crest stem cells (NCSCs), a type of multipotent stem cells, are more easily obtained than mesenchymal stem cells. We hypothesize that NCSC-CM has anti-inflammatory properties that could protect against IR-induced lung injury in rats. In this study, NCSC-CM was derived from rat NCSCs. Typical acute lung injury was induced by 30-min ischemia followed by 90-min reperfusion in adult male Sprague-Dawley rats. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to analyze the degree of lung injury after the experiment. NCSC-CM was administered before ischemia and after reperfusion. NCSC-CM treatment significantly attenuated IR-induced lung edema, as indicated by decreases in pulmonary vascular permeability, lung weight gain, wet to dry weight ratio, lung weight to body weight ratio, pulmonary arterial pressure, and protein level in BALF. The levels of tumor necrosis factor-α and interleukin-6 in the BALF were also significantly decreased. Additionally, NCSC-CM improved lung pathology and neutrophil infiltration in the lung tissue, and significantly suppressed nuclear factor (NF)-κB activity and IκB-α degradation in the lung. However, heating NCSC-CM eliminated these protective effects. Our experiment demonstrates that NCSC-CM treatment decreases IR-induced acute lung injury and that the protective mechanism may be attributable to the inhibition of NF-κB activation and the inflammatory response. Therefore, NCSC-CM may be a novel approach for treating IR-induced lung injury.

Background Previous investigations reveal that BTP2, a store-operated calcium channel blocker, has protective and anti-inflammatory properties in multiple inflammatory diseases. This study investigates whether BTP2 can protect against decompression sickness (DCS) in a rat model. Methods BTP2 (2 mg/kg) was administered to male Sprague-Dawley rats 30 min before subjecting them to hyperbaric pressure. Control rats were not treated. After decompression, signs of DCS were examined, and samples of bronchoalveolar lavage fluid and lung tissue were obtained for evaluation. Results The incidence and mortality of DCS were decreased significantly in rats treated with BTP2 compared to those treated with dimethyl sulfoxide. BTP2 significantly attenuated DCS-induced lung edema, histological evidence of lung inflammation, necroptosis, and apoptosis, while it decreased levels of tumor necrosis factor alpha, interleukin-6, and cytokine-induced neutrophil chemoattractant-1 in bronchoalveolar lavage fluid. In addition, BTP2 reduced the expression of nuclear factor of activated T cells and early growth response protein 3 in lung tissue. BTP2 also significantly increased the levels of inhibitor kappa B alpha and suppressed the levels of nuclear factor kappa B in lung tissue. Conclusion The results suggest that BTP2 may has potential as a prophylactic therapy to attenuate DCS-induced injury.

Various animal studies have shown beneficial effects of hypercapnia in lung injury. However, in patients with acute respiratory distress syndrome (ARDS), there is controversial information regarding the effect of hypercapnia on outcomes. The duration of carbon dioxide inhalation may be the key to the protective effect of hypercapnia. We investigated the effect of pre-treatment with inhaled carbon dioxide on lipopolysaccharide (LPS)-induced lung injury in mice. C57BL/6 mice were randomly divided into a control group or an LPS group. Each LPS group received intratracheal LPS (2 mg/kg), the LPS groups were exposed to hypercapnia (5% carbon dioxide) for 10 min or 60 min before LPS. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. LPS significantly increased the ratio of lung weight to body weight, concentrations of BALF protein, tumor necrosis factor-&alpha, and CXCL2, protein carbonyls, neutrophil infiltration, and lung injury score. LPS induced the degradation of the inhibitor of nuclear factor-&kappa, B-&alpha, (I&kappa, ) and nuclear translocation of NF-&kappa, B. LPS increased the surface protein expression of toll-like receptor 4 (TLR4). Pre-treatment with inhaled carbon dioxide for 10 min, but not for 60 min, inhibited LPS-induced pulmonary edema, inflammation, oxidative stress, lung injury, and TLR4 surface expression, and, accordingly, reduced NF-&kappa, B signaling. In summary, our data demonstrated that pre-treatment with 10-min carbon dioxide inhalation can ameliorate LPS-induced lung injury. The protective effect may be associated with down-regulation of the surface expression of TLR4 in the lungs.

Aims: Obstructive sleep apnea (OSA) and insomnia commonly coexist; hypnotics are broadly prescribed for insomnia therapy. However, the safety of hypnotics use in OSA patients is unclear. We conducted a retrospective case-control study to investigate the risk of adverse respiratory events in hypnotics-using OSA patients.Methods: We obtained data from the Taiwan National Health Insurance Database from 1996 to 2013. The case group included 216 OSA patients with newly diagnosed adverse respiratory events, including pneumonia and acute respiratory failure. The control group included OSA patients without adverse respiratory events, which was randomly frequency-matched to the case group at a 1:1 ratio according to age, gender, and index year. Hypnotics exposure included benzodiazepines (BZD) and non-benzodiazepines (non-BZD). A recent user was defined as a patient who had taken hypnotics for 1–30 days, while a long-term user was one who had taken hypnotics for 31–365 days.Results: Multivariable adjusted analysis showed recent BZD use is an independent risk for adverse respiratory events (OR = 2.70; 95% CI = 1.15–6.33; P < 0.001). Subgroup analysis showed both recent and long-term BZD use increased the risk of acute respiratory failure compared to never BZD use (OR = 28.6; 95% CI = 5.24–156; P < 0.001, OR = 10.1; 95% CI = 1.51–67.7; P < 0.05, respectively). Neither BZD nor non-BZD use increased the risk of pneumonia in OSA patients.Conclusion: BZD use might increase the risk of acute respiratory failure in OSA patients.

Annexin A1 (AnxA1) is an endogenous protein that modulates anti-inflammatory processes, and its therapeutic potential has been reported in a range of inflammatory diseases. The effect of AnxA1 on ischemia-reperfusion (IR)-induced lung injury has not been examined. In this study, isolated, perfused rat lungs were subjected to IR lung injury induced by ischemia for 40 min, followed by reperfusion for 60 min. The rat lungs were randomly treated with vehicle (phosphate-buffered saline), and Ac2-26 (an active N-terminal peptide of AnxA1) with or without an

Methotrexate has immunosuppressive effects and is administered for refractory chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a patient with refractory chronic urticaria managed by low-dose weekly methotrexate treatment (total cumulative dose 195mg). Our study highlights the importance of providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in patients with chronic urticaria under methotrexate therapy.

Stanniocalcin-1 (STC1) is an endogenous glycoprotein whose anti-inflammatory effects occur through induction of uncoupling proteins to reduce oxidative stress. In this study, we tested the hypothesis that exogenous recombinant human STC1 (rhSTC1) protects against lipopolysaccharide (LPS)-induced acute lung injury in mice. Anesthetized C57BL/6 mice underwent intratracheal spraying of LPS (20 µg/10 g body wt), and lung injury was assessed 24h later by analyzing pulmonary edema, bronchoalveolar lavage fluid, and lung histopathology. Lung inflammation, oxidative stress, and expression of STC1 and its downstream uncoupling protein 2 (UCP2) were analyzed at specific time points. Expression of UCP2 was suppressed initially but was subsequently upregulated after STC1 elevation in response to intratracheal administration of LPS. Intratracheal rhSTC1 treatment 1h before or after LPS spraying significantly attenuated pulmonary inflammation, oxidative stress, cell apoptosis, and acute lung injury. Pretreatment with STC1 short interfering RNA 48 h before LPS spraying inhibited the expression of STC1 and UCP2 and significantly increased the extent of lung injury. These findings suggest that STC1 is an endogenous stress protein that may counteract LPS-induced lung injury by inhibiting the inflammatory cascade and inducing antioxidant and antiapoptotic mechanisms. However, the potential clinical application of STC1 and the direct linkage between UCP2 and LPS-induced lung injury remain to be further investigated.

Ischemia-reperfusion (IR)-induced acute lung injury (ALI) is implicated in several clinical conditions including lung transplantation, cardiopulmonary bypass surgery, re-expansion of collapsed lung from pneumothorax or pleural effusion and etc. IR-induced ALI remains a challenge in the current treatment. Carbonic anhydrase has important physiological function and influences on transport of CO2. Some investigators suggest that CO2 influences lung injury. Therefore, carbonic anhydrase should have the role in ALI. This study was undertaken to define the effect of a carbonic anhydrase inhibitor, acetazolamide (AZA), in IR-induced ALI, that was conducted in a rat model of isolated-perfused lung with 30 minutes of ischemia and 90 minutes of reperfusion. The animals were divided into six groups (n = 6 per group): sham, sham + AZA 200 mg/kg body weight (BW), IR, IR + AZA 100 mg/kg BW, IR + AZA 200 mg/kg BW and IR+ AZA 400 mg/kg BW. IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, pulmonary hypertension, neutrophilic sequestration, and an increase in the expression of pro-inflammatory cytokines. Increases in carbonic anhydrase expression and perfusate pCO2 levels were noted, while decreased Na-K-ATPase expression was noted after IR. Administration of 200mg/kg BW and 400mg/kg BW AZA significantly suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1, IL-6 and IL-17) and attenuated IR-induced lung injury, represented by decreases in pulmonary hyper-permeability, pulmonary edema, pulmonary hypertension and neutrophilic sequestration. AZA attenuated IR-induced lung injury, associated with decreases in carbonic anhydrase expression and pCO2 levels, as well as restoration of Na-K-ATPase expression.

Background Emerging evidence reveals that nicotinamide phosphoribosyltransferase (NAMPT) has a significant role in the pathophysiology of the inflammatory process. NAMPT inhibition has a beneficial effect in the treatment of a variety of inflammatory diseases. However, it remains unclear whether NAMPT inhibition has an impact on ischemia-reperfusion (I/R)-induced acute lung injury. In this study, we examined whether NAMPT inhibition provided protection against I/R lung injury in rats. Methods Isolated perfused rat lungs were subjected to 40 min of ischemia followed by 60 min of reperfusion. The rats were randomly allotted to the control, control + FK866 (NAMPT inhibitor, 10 mg/kg), I/R, or I/R + FK866 groups (n = 6 per group). The effects of FK866 on human alveolar epithelial cells exposed to hypoxia-reoxygenation (H/R) were also investigated. Results Treatment with FK866 significantly attenuated the increases in lung edema, pulmonary arterial pressure, lung injury scores, and TNF-α, CINC-1, and IL-6 concentrations in bronchoalveolar lavage fluid in the I/R group. Malondialdehyde levels, carbonyl contents and MPO-positive cells in lung tissue were also significantly reduced by FK866. Additionally, FK866 mitigated I/R-stimulated degradation of IκB-α, nuclear translocation of NF-κB, Akt phosphorylation, activation of mitogen-activated protein kinase, and downregulated MKP-1 activity in the injured lung tissue. Furthermore, FK866 increased Bcl-2 and decreased caspase-3 activity in the I/R rat lungs. Comparably, the in vitro experiments showed that FK866 also inhibited IL-8 production and NF-κB activation in human alveolar epithelial cells exposed to H/R. Conclusions Our findings suggest that NAMPT inhibition may be a novel therapeutic approach for I/R-induced lung injury. The protective effects involve the suppression of multiple signal pathways.

Objectives Ischemia–reperfusion acute lung injury is characterized by increased vascular permeability, lung edema, and neutrophil sequestration. Ischemia–reperfusion acute lung injury occurs in lung transplantation and other major surgical procedures. Effective regulation of alveolar fluid balance is critical for pulmonary edema. Sodium-potassium-chloride co-transporter regulates alveolar fluid and is associated with inflammation. We hypothesized that sodium-potassium-chloride co-transporter is important in ischemia–reperfusion acute lung injury. Bumetanide, a sodium-potassium-chloride co-transporter inhibitor, is used to treat pulmonary edema clinically. We studied the effect of bumetanide in ischemia–reperfusion acute lung injury. Methods Isolated perfusion of mouse lungs in situ was performed. The main pulmonary artery and left atrium were catheterized for lung perfusion and effluent collection for recirculation, respectively, with perfusate consisting of 1 mL blood and 9 mL physiologic solution. Ischemia–reperfusion was induced by 120 minutes of ischemia (no ventilation or perfusion) and reperfused for 60 minutes. Wild-type, SPAK knockout (SPAK −/− ), and WNK4 knockin (WNK4 D561A/+ ) mice were divided into control, ischemia–reperfusion, and ischemia–reperfusion + bumetanide groups (n = 6 per group). Bumetanide was administered via perfusate during reperfusion. Measurements were taken of lung wet/dry weight, microvascular permeability, histopathology, cytokine concentrations, and activity of the nuclear factor-κB pathway. Results In wild-type mice, ischemia–reperfusion caused lung edema (wet/dry weight 6.30 ± 0.36) and hyperpermeability (microvascular permeability, 0.29 ± 0.04), neutrophil sequestration (255.0 ± 55.8 cells/high-power field), increased proinflammatory cytokines, and nuclear factor-κB activation (1.33 ± 0.13). Acute lung injury was more severe in WNK4 mice with more lung edema, permeability, neutrophil sequestration, and nuclear factor-κB activation. Severity of acute lung injury was attenuated in SPAK −/− mice. Bumetanide decreased pulmonary edema (wild-type: wet/dry weight 5.05 ± 0.44, WNK4: wet/dry weight 5.13 ± 0.70), neutrophil sequestration (wild-type: 151.7 ± 27.8 cells/high-power field, WNK4: 135.3 ± 19.1 cells/high-power field), permeability (wild-type: 0.19 ± 0.01, WNK4: 0.21 ± 0.03), cytokines, and nuclear factor-κB activation after ischemia–reperfusion. Conclusions Functional reduction of sodium-potassium-chloride co-transporter by genetic or pharmacologic treatment to inhibit sodium-potassium-chloride co-transporter resulted in lower severity of acute lung injury induced by ischemia–reperfusion. Sodium-potassium-chloride co-transporter may present a promising target for therapeutic interventions in a clinical setting.

Annexin A1 (AnxA1) is an endogenous protein that modulates anti-inflammatory processes, and its therapeutic potential has been reported in a range of inflammatory diseases. The effect of AnxA1 on ischemia-reperfusion (IR)-induced lung injury has not been examined. In this study, isolated, perfused rat lungs were subjected to IR lung injury induced by ischemia for 40 min, followed by reperfusion for 60 min. The rat lungs were randomly treated with vehicle (phosphate-buffered saline), and Ac2-26 (an active N-terminal peptide of AnxA1) with or without an N-formyl peptide receptor (FPR) antagonist N-Boc-Phe-Leu-Phe-Leu-Phe (Boc2). An in vitro study of the effects of Ac2-26 on human alveolar epithelial cells subjected to hypoxia-reoxygenation was also investigated. Administration of Ac2-26 in IR lung injury produced a significant attenuation of lung edema, pro-inflammatory cytokine production recovered in bronchoalveolar lavage fluid, oxidative stress, apoptosis, neutrophil infiltration, and lung tissue injury. Ac2-26 also decreased AnxA1 protein expression, inhibited the activation of nuclear factor-κB and mitogen-activated protein kinase pathways in the injured lung tissue. Finally, treatment with Boc2 abolished the protective action of Ac2-26. The results indicated that Ac2-26 had a protective effect against acute lung injury induced by IR, which may be via the activation of the FPR.

Background Evidence reveals that hypercapnic acidosis (HCA) modulates immune responses. However, the effect of HCA on allogenic skin graft rejection is unknown. We examined whether HCA might improve skin graft survival in a mouse model of skin transplantation. Methods A major histocompatibility-complex-incompatible BALB/c to C57BL/6 mouse skin transplantation model was used. Animals were divided into sham control, air, and HCA groups. Mice in the HCA group were exposed daily to 5% CO 2 in air for 1 h. Skin grafts were harvested for histologic analyses. Nuclear factor (NF)-κB activation was determined in harvested draining lymph nodes. Spleen weights and serum levels of tumor necrosis factor-α and chemokine (C-X-C motif) ligand 2 were serially assessed after skin transplantation. Results Skin allografts survived significantly longer in the HCA group of mice than those in the air group. Allografted mice in the air group underwent a 2.1-fold increase in spleen weight compared with a 1.1-fold increase in the mice with HCA on day 3. There were increased inflammatory cell infiltration, folliculitis, focal dermal–epidermal separation, and areas of epidermal necrosis in the air group that were reduced with HCA treatment. In the HCA group, CD8 + T cell infiltration at day 7 decreased significantly but not CD4 + T cell infiltration. In addition, HCA significantly suppressed serum tumor necrosis factor-α on days 1 and 3 and chemokine (C-X-C motif) ligand 2 on days 1 and 10. Furthermore, the HCA group had remarkably suppressed NF-κB activity in draining lymph nodes. Conclusions HCA significantly prolonged the survival of incompatible skin allografts in mice by reducing proinflammatory cytokine production, immune cell infiltration, and NF-κB activation.