Pulmonary Recruitment Research Articles

Pain after laparoscopic surgery: Focus on shoulder-tip pain after gynecological laparoscopic surgery.

Laparoscopy, one of minimally invasive procedures, is a commonly used procedure in diagnosis and management of various kinds of clinical problems, including gynecologic organ-related diseases. Compared with conventional exploratory laparotomy, the benefits of laparoscopic surgery include reduction of surgical wound, decreasing in postoperative pain, shortening hospital stay, rapid recovery, and a better cosmetic result. However, there are still up to 80% of patients after laparoscopic surgery complaining of high levels of pain and needing pain relief. Postlaparoscopic pain can be separated into distinct causes, such as surgical trauma- or incision wound-associated inflammatory change, and pneumoperitoneum (carbon dioxide [CO2])-related morphological and biochemical changes of peritoneum and diaphragm. The latter is secondary to irritation, stretching, and foreign body stimulation, leading to phrenic neuropraxia and subsequent shoulder-tip pain (STP). STP is the most typical unpleasant experience of patients after laparoscopic surgery. There are at least 11 strategies available to attempt to decrease postlaparoscopic STP, including (1) the use of an alternative insufflating gas in place of CO2, (2) the use of low-pressure pneumoperitoneum in place of standard-pressure pneumoperitoneum, (3) the use of warmed or warmed and humidified CO2, (4) gasless laparoscopy, (5) subdiaphragmatic intraperitoneal anesthesia, (6) local intraperitoneal anesthesia, (7) actively expelling out of gas, (8) intraperitoneal drainage, (9) fluid instillation, (10) pulmonary recruitment maneuvers, and (11) others and combination. The present article is limited in discussing postlaparoscopic STP. We extensively review published articles to provide a better strategy to reduce postlaparoscopic STP.

Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin-induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.

Pulmonary immunosuppression often occurs after burn injury (BI). However, the reasons for BI-induced pulmonary immunosuppression are not clearly understood. Neutrophil recruitment and neutrophil extracellular trap (NET) formation (NETosis) are important components of a robust pulmonary immune response, and we hypothesized that pulmonary inflammation and NETosis are defective after BI. To test this hypothesis, we established a mouse model with intranasal LPS instillation in the presence or absence of BI (15% of body surface burn) and determined the degree of immune cell infiltration, NETosis, and the cytokine levels in the airways and blood on d 2. Presence of LPS recruited monocytes and large numbers of neutrophils to the airways and induced NETosis (citrullinated histone H3, DNA, myeloperoxidase). By contrast, BI significantly reduced LPS-mediated leukocyte recruitment and NETosis. This BI-induced immunosuppression is attributable to the reduction of chemokine (C-C motif) ligand (CCL) 2 (monocyte chemoattractant protein 1) and CCL3 (macrophage inflammatory protein 1α). BI also suppressed LPS-induced increase in IL-17A, IL-17C, and IL-17E/IL-25 levels in the airways. Therefore, BI-mediated reduction in leukocyte recruitment and NETosis in the lungs are attributable to these cytokines. Regulating the levels of some of these key cytokines represents a potential therapeutic option for mitigating BI-mediated pulmonary immunosuppression.-Sakuma, M., Khan, M. A. S., Yasuhara, S., Martyn, J. A., Palaniyar, N. Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin-induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.

Short-term high-fat diet feeding protects from the development of experimental allergic asthma in mice.

A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short-term high-fat diet (HFD) feeding on the development of allergic asthma. To delineate the impact of short-term HFD feeding on the development of experimental allergic asthma. Female C57BL/6JRJ mice were fed with a short-term HFD or chow diet (CD) for 12weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)-mediated activation of T cells. Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD-fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD-fed mice. Mucus production was similar in both treatment groups. OVA-induced increases in DC and CD4+ T-cell recruitment to the lungs were significantly attenuated in HFD-fed mice. MHC-II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD-fed compared to CD-fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation. These findings suggest that short-term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC-II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short-term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.

The Strategy of "Pulmonary Opening by Titration of Positive End-expiratory Pressure" Means of a Pulmonary Recruitment Maneuver in Patients With Acute Respiratory Distress Syndrome: for Which Patients?

The Strategy of "Pulmonary Opening by Titration of Positive End-expiratory Pressure" Means of a Pulmonary Recruitment Maneuver in Patients With Acute Respiratory Distress Syndrome: for Which Patients?

Osteopontin mediates murine transfusion-related acute lung injury via stimulation of pulmonary neutrophil accumulation

AbstractTransfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related fatalities and is characterized by the onset of acute respiratory distress within 6 hours upon blood transfusion. Specific therapies are unavailable. Preexisting inflammation is a risk factor for TRALI and neutrophils (polymorphonuclear neutrophils [PMNs]) are considered to be the major pathogenic cells. Osteopontin (OPN) is a multifunctional protein expressed at sites of inflammation and, for example, is involved in pulmonary disorders, can regulate cellular migration, and can function as a PMN chemoattractant. We investigated whether OPN is involved in TRALI induction by promoting PMN recruitment to the lungs. Using a previously established murine TRALI model, we found that in contrast to wild-type (WT) mice, OPN knockout (KO) mice were resistant to antibody-mediated PMN-dependent TRALI induction. Administration of purified OPN to the OPN KO mice, however, restored the TRALI response and pulmonary PMN accumulation. Alternatively, blockade of OPN in WT mice using an anti-OPN antibody prevented the onset of TRALI induction. Using pulmonary immunohistochemistry, OPN could be specifically detected in the lungs of mice that suffered from TRALI. The OPN-mediated TRALI response seemed dependent on macrophages, likely the cellular source of OPN and OPN polymerization, and independent from the OPN receptor CD44, interleukin 6 (IL-6), and other PMN chemoattractants including macrophage inflammatory protein-2 (MIP-2). These data indicate that OPN is critically required for induction of antibody-mediated murine TRALI through localization to the lungs and stimulation of pulmonary PMN recruitment. This suggests that anti-OPN antibody therapy may be a potential therapeutic strategy to explore in TRALI patients.

Pulmonary capillary surface area in supine exercising humans: demonstration of vascular recruitment.

In exercising humans, cardiac output (CO) increases, with minor increases in pulmonary artery pressure (PAP). It is unknown if the CO is accommodated via distention of already perfused capillaries or via recruitment of nonconcomitantly perfused pulmonary capillaries. Ten subjects (9 female) performed symptom-limited exercise. Six had resting mean PAP (PAPm) <20 mmHg, and four had PAPm between 21 and 24 mmHg. The first-pass pulmonary circulatory metabolism of [3H]benzoyl-Phe-Ala-Pro (BPAP) was measured at rest and at peak exercise, and functional capillary surface area (FCSA) was calculated. Data are means ± SD. Mean pulmonary arterial pressure rose from 18.8 ± 3.3 SD mmHg to 28.5 ± 4.6 SD mmHg, CO from 6.4 ± 1.6 to 13.4 ± 2.9 L/min, and pulmonary artery wedge pressure from 14 ± 3.3 to 19.5 ± 5 mmHg (all P ≤ 0.001). Percent BPAP metabolism fell from 74.7 ± 0.1% to 67.1 ± 0.1%, and FCSA/body surface area (BSA) rose from 2,939 ± 640 to 5,018 ± 1,032 mL·min-1·m-2 (all P < 0.001). In nine subjects, the FCSA/BSA-to-CO relationship suggested principally capillary recruitment and not distention. In subject 10, a marathon runner, resting CO and FCSA/BSA were high, and increases with exercise suggested distention. Exercising humans demonstrate pulmonary capillary recruitment and distention. At moderate resting CO, increasing blood flow causes principally recruitment while, based on one subject, when exercise begins at high CO, further increases appear to cause distention. Our findings clarify an important physiologic question. The technique may provide a means for further understanding exercise physiology, its limitation in pulmonary hypertension, and responses to therapy.

Embedding research recruitment in a community resource e-prescribing system: lessons from an implementation study on Chicago's South Side.

The study sought to implement and assess the CommunityRx e-prescribing system to recruit research participants from a predominantly non-Hispanic Black community on Chicago's South Side. CommunityRx integrates with electronic medical record systems to generate a personalized list of health-promoting community resources (HealtheRx). Between December 2015 and December 2016, HealtheRxs distributed at outpatient visits to adults with asthma or chronic obstructive pulmonary disease also incentivized participation in a pulmonary research registry. Usual practices for registry recruitment continued in parallel. Focus groups established acceptability and appropriateness among the target population. Pulmonary research registry recruitment information was included on 13437 HealtheRxs. Forty-one (90% non-Hispanic Black) patients responded with willingness to participate and 9 (8 non-Hispanic Black) returned a signed consent required to enroll. Usual recruitment practices enrolled 4 registrants (1 non-Hispanic Black). Automating research recruitment using a community e-prescribing system is feasible. Implementation of an electronic medical record-integrated, community resource referral tool promotes enrollment of eligible underrepresented research participants; however, enrollment was low.

Comparison of Intraperitoneal Normal Saline Infusion with Pulmonary Recruitment Maneuver in Reducing Shoulder and Upper Abdomen Pain Following Gynecologic Laparoscopic Procedures: A Randomized, Controlled, Triple-Blind Trial.

ObjectivesThe current study aimed at evaluating the effect of intraperitoneal infusion of normal saline (NS) and pulmonary recruitment maneuver (PRM) on the reduction of pain in shoulder, upper abdomen, and incision site after elective laparoscopic gynecologic surgery.MethodsTotally, 280 patients (mean age: 30.5 years) that underwent laparoscopic gynecologic surgery from October 2013 to August 2015 were randomly and equally allocated into four groups. Group A received intraperitoneal infusion of NS 1.5 - 2 mL/kg of body weight; group B received PRM with five manual pulmonary inflations at a maximum pressure of 60 cm H2O; group C simultaneously received two former interventions; and finally the control group D received routine method of gentle abdominal pressure. All patients were assessed in the first 24 hours after surgery.ResultsThere was an unsteady pattern for pain in shoulder, upper abdomen, and incision site at different time points across the studied groups over the trial. Patients in group B showed significantly lower shoulder pain 24 hours after laparoscopic gynecologic surgery (P = 0.01), while patients in group D had significantly lower incision site pain (P < 0.001).ConclusionsPRM was superior to intraperitoneal infusion of NS for reducing pain in the first 24 hours after laparoscopic gynecologic surgery.

Pulmonary Recruitment Maneuver With 15 and 30 cmH2O Pressure to Reduce the Postoperative Shoulder Pain

Pulmonary Recruitment Maneuver With 15 and 30 cmH2O Pressure to Reduce the Postoperative Shoulder Pain

Anti-inflammatory Property of Galectin-1 in a Murine Model of Allergic Airway Inflammation.

Galectin-1 (Gal-1) has immunomodulatory activities in various allergic inflammatory disorders, but its potential anti-inflammatory properties on allergic airway diseases have not been confirmed. We explored the pharmacological effects of Gal-1 on the progression of allergic airway inflammation and investigated the underlying mechanism. Female C57BL/6 mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14-17 to establish an allergic airway inflammation model. In the challenge phase, a subset of mice was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). We found that rGal-1 inhibited pulmonary inflammatory cell recruitment, mucus secretion, bronchoalveolar lavage fluid (BALF) inflammatory cell infiltration, and cytokine production. The treatment also suppressed the infiltration of eosinophils into the allergic lung as indicated by decreased expression levels of eotaxin and eosinophil peroxidase (EPX). However, only the expression levels of IL-25, neither IL-33 nor TSLP, were significantly decreased in the lung by rGal-1 treatment. These immunomodulatory effects in the allergic lung were correlated with the activation of extracellular signal-regulated kinase (ERK) signaling pathway and downregulation of endogenous Gal-1. In addition, rGal-1 reduced the plasma concentrations of anti-OVA immunoglobulin E (IgE) and IL-17. Our findings suggest that rGal-1 is an effective therapy for allergic airway inflammation in a murine model and may be a potential pharmacological target for allergic airway inflammatory diseases.

Multi-Modal Analgesic Technique for Pain Control in Patients Undergoing Diagnostic Gynecological Laparoscopy: Randomized Controlled Clinical Trial.

BACKGROUND:Advancement in minimally invasive laparoscopic surgeries make it one of the best choices for both the surgeon and the patient. The anesthesiologist had to improve the techniques used to control post-operative pain.AIM:In this study, we hyposethized that multi-modal analgesic technique which is a combination of two simple techniques (intraperitoneal lidocaine and pulmonary recruitment) allow better result than using only one of them.PATIENTS AND METHOD:This randomised controlled, double-blind study was conducted in Kasr-Alainy hospital, faculty of medicine, Cairo University, Egypt from September 2017 till February 2018. Fifty female patients, scheduled for diagnostic gynecologic laparoscopy were included in the study. Patients were randomly allocated using random computer allocation with numbered closed opaque envelopes into four study group. GM (n = 12): Patients received pulmonary recruitment maneuver and intra-peritoneal Lidocaine, GL (n = 13): Patients received intra-peritoneal Lidocaine, GP (n = 13): Patients received Pulmonary Recruitment Maneuver, GC (n = 12): Patients received passive exsufflation through the port site. In the ward, patients were asked to fulfil a questionnaire about pain severity using (VAS) at 1, 3, 6-hour post-operative both the patients and the anesthesiologist that assess the (VAS) were blind of the patient groupRESULTS:Regarding pain score between groups VAS 1 (the primary outcome) was lowest in GM {4.5 (3-5)} in comparison with other groups (P value = 0.015), while VAS 3 & VAS 6 wasn’t statistically significant between groups. Regarding Time of first rescue analgesia; GM {3 (1.75-4)} showed the longest time in between groups (P-value = 0.042). As regard nausea and vomiting; there was no statistically significant difference in in-between groups.CONCLUSION:Application of Multi-modal analgesic technique allows better analgesia for a longer duration than the use of the sole technique for control of abdominal pain in patients undergoing diagnostic gynaecological laparoscopy.

Mouse model to study pulmonary intravascular macrophage recruitment and lung inflammation in acute necrotizing pancreatitis.

Patients suffering from severe acute pancreatitis (AP) can develop acute lung injury (ALI) with poor outcomes and the mechanisms involved remain incompletely understood. Pulmonary intravascular macrophages (PIMs), which are credited as promoters of ALI, are not constitutively present in humans and rodents; however, there is evidence of PIM recruitment in rodents during some pathological conditions, such as hepatic diseases. Therefore, this study assesses PIM recruitment in the lungs of a mouse model of acute necrotizing pancreatitis (ANP) induced with L-arginine monohydrochloride. Mice were euthanized after 24h, 72h and 120h. Control mice received sham injections of saline. Pancreatic histopathological grading and plasma amylase were used to confirm the development of ANP in L-arginine-treated mice. Histopathological grading of lungs from the ANP mice at 72h showed increased mononuclear phagocytes in alveolar septa, compared to that from the controls. Lungs from the ANP mice also showed increased numbers of CD68-immunopositive alveolar septal macrophages, suggestive of PIM recruitment, compared to those from the controls. Lungs from the ANP mice showed increased expression of IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1) and von Willebrand factor compared to those from the controls. The recruitment of CD68-positive septal macrophages was not observed in MCP-1 knockout mice with ANP at 72h when compared to C57BL/6 wild-type mice. Taken together, we developed a mouse model of PIM recruitment dependent on MCP-1 that allows us to explore their roles in ANP-associated ALI.

Assessment of a Combination of Clinical Maneuvers in Evaluation of Post-Laparoscopic Pain: A Randomized Clinical Trial.

To assess the efficacy of the combined maneuvers in evaluation of post-laparoscopic pain. A randomized controlled study was conducted. Sixty-four women were included in the study and were randomly divided into two groups. Intervention group received combined maneuvers such as intraperitoneal normal saline infusion, pulmonary recruitment maneuver and local bupivacaine instillation at port sites after laparoscopic surgery. Control group received routine care. Upper abdominal pain, shoulder pain and incision site pain were noted in both groups at 3, 6, 12, 24 and 48h postoperatively. The median interquartile range (in centiles) of upper abdominal pain score 3, 6 and 12h postoperatively in the intervention group was 1.0 (0.25-1.0), 1.0 (0.0-1.0) and 0.50 (0.0-1.0), and in the control group, the values were 2.0 (2.0-1.0), 2.0 (2.0-1.0) and 1.0 (0-1.0) at 3, 6 and 12h, respectively (p < 0.000). The median interquartile range of shoulder pain score 3, 6 and 12h postoperatively in the intervention group was 0.0 (0.0-1.0), 0.0 (0.0-0.75) and 0.0 (0.0-1.0), and in the control group, the values were 1.0 (0.0-2.0), 1.0 (0.0-1.75) and 1.0 (0-1.0) at 3, 6, and 12h. The upper abdominal pain and shoulder pain relief was significantly more in the intervention group than in the control group in the first 12h of surgery. Combined maneuvers could significantly reduce post-laparoscopic upper abdominal and shoulder pain.Clinical Trial CTRI Registration Number-CTRI/2017/07/0089, web address of CTRI-http://ctri.nic.in.

Differential severity of LPS-induced lung injury in CD26/DPP4 positive and deficient F344 rats.

Lipopolysaccharide (LPS) induced inflammation often leads to lung injury, in which pulmonary recruitment of neutrophils plays a pivotal role. Inflammatory processes are influenced by CD26/DPP4, highly expressed in lungs. Asthma induced CD26/DPP4 deficient (CD26/DPP4⁻) Fischer (F) 344 rats suffering from a transport block in the rER caused by a point mutation showed reduced pulmonary inflammation and reduced expression of immunomodulating surfactant proteins (SP). The degree of LPS induced lung injury in CD26/DPP4 deficient rats has not been investigated so far. We hypothesize that LPS induced lung injury leads not only to an attenuated inflammation but also to a reduced SP expression and decreased structural damage in CD26/DPP4⁻ rats. Both genotypes were intratracheally instilled with 250 µl LPS or with 250 µl 0.9% NaCl. Nine hours later animals were killed and either bronchoalveolar lavage was carried out to determine inflammatory cells and surface tension or lung blocks were removed and processed for histology, immunohistochemistry, electron microscopy or qRt-PCR analyses and Western Blot analyses. Signs of acute lung injury, such as structural damage of the blood gas barrier occurred only sporadically in both genotypes. LPS-induced CD26/DPP4⁻ rats showed decreased gene expression of SP-A and SP-D and reduced signs of lung inflammation associated with a reduced alveolar influx of macrophages and neutrophils. Less pulmonary inflammation combined with less structural alterations and minor expression of immunomodulating SP may be an indication of the critical role of CD26/DPP4 in regulating lung inflammation.

Semi-Fowler positioning in addition to the pulmonary recruitment manoeuvre reduces shoulder pain following gynaecologic laparoscopic surgery.

IntroductionThe semi-Fowler position, defined as a body position at 30° head-of-bed elevation, has been shown to increase intra-abdominal pressure.AimTo investigate the impact of semi-Fowler positioning in addition to the pulmonary recruitment manoeuvre (PRM) on post-laparoscopic shoulder pain.Material and methodsOne hundred and six patients (mean age: 43 ±12 years) undergoing gynaecologic laparoscopic surgery (LS) were included. The patients were divided into three groups: group 1 consisted of patients receiving PRM in the neutral position, group 2 comprised patients receiving PRM in the semi-Fowler position, and patients in the control group received neither PRM nor additional positioning. Information concerning wound and shoulder pain (post-laparoscopic shoulder pain – PLSP) at postoperative 6, 12 and 24 h was recorded using a visual analogue scale (VAS) for each patient.ResultsThe PLSP scores at postoperative 6 h (5.71 ±0.86, 5.28 ±0.84 and 6.61 ±0.91, respectively, p < 0.001), 12 h (4.41 ±0.83, 4.01 ±0.82 and 5.32 ±0.97, respectively, p < 0.001), and 24 h (3.24 ±0.78, 2.44 ±0.73 and 4.34 ±0.85, respectively, p < 0.001) were significantly different among the groups, the lowest being in those who received PRM in addition to semi-Fowler positioning.ConclusionsSemi-Fowler positioning in addition to PRM significantly reduces post-laparoscopic shoulder pain. We assume that the benefit gained using the semi-Fowler positioning is mainly derived from its potential to better evacuate the remaining abdominal gas following LS.

Monocytes Represent One Source of Bacterial Shielding from Antibiotics following Influenza Virus Infection.

Methicillin-resistant Staphylococcus aureus has emerged as a significant contributor to morbidity and mortality associated with influenza infection. In this study, we show in a mouse model that preceding influenza infection promotes S. aureus resistance to killing by antibiotics. This resistance coincides with influenza-induced accumulation of inflammatory monocytes in the lung. CCR type 2 (CCR2) is responsible for pulmonary monocyte recruitment after influenza infection. We found that antibiotic-treated Ccr2-deficient (Ccr2-/-) mice exhibit significantly improved bacterial control and survival from influenza and methicillin-resistant S. aureus coinfection, despite a delay in viral clearance. Mechanistically, our results from in vivo studies indicate that influenza-induced monocytes serve as reservoirs for intracellular S. aureus survival, thereby promoting bacterial resistance to antibiotic treatment. Blocking CCR2 with a small molecular inhibitor (PF-04178903), in conjunction with antibiotic treatment, enhanced lung bacterial clearance and significantly improved animal survival. Collectively, our study demonstrates that inflammatory monocytes constitute an important and hitherto underappreciated mechanism of the conflicting immune requirements for viral and bacterial clearance by hosts, which subsequently leads to exacerbated outcomes of influenza and S. aureus coinfection.

Effect of Low-pressure Pulmonary Recruitment Maneuver on Postlaparoscopic Shoulder Pain: Randomized Controlled Trial

Study ObjectivePostlaparoscopic shoulder pain (PLSP) is effectively reduced by a pulmonary recruitment maneuver (PRM). The goal of this study is to assess the efficacy of a PRM using maximal inspiratory pressure of 30 cm H2O, which is lower than previously studied pressure for reducing PLSP. DesignRandomized controlled trial. SettingUniversity hospital. PatientsEighty-four patients who were undergoing elective gynecologic laparoscopy. InterventionsPatients were randomly assigned to the control (n = 42) or the PRM (n = 42) group. Measurements and Main ResultsThe primary outcome was the intensity of the shoulder pain using the visual analog scale (VAS). The VAS score of shoulder pain (median [interquartile range]) was significantly lower in the PRM group than in the control group at 24 hours (0 [0–0] vs 1.5 [0–4.0], p <.001) and 48 hours (0 [0–0] vs 1.0 [0–2.0], p <.001) after surgery. Other variables, including surgical pain score and vital signs, were similar between the 2 groups. ConclusionThe PRM with 30 cm H2O can be a simple method to reduce PLSP. Therefore, it would be helpful to perform the PRM with 30 cm H2O routinely.

Interventions to reduce shoulder pain following gynaecological laparoscopic procedures.

Interventions to reduce shoulder pain following gynaecological laparoscopic procedures.

Batf2 differentially regulates tissue immunopathology in Type 1 and Type 2 diseases

SUMMARYBasic leucine zipper transcription factor 2 (Batf2) activation is detrimental in Type 1-controlled infectious diseases, demonstrated during infection with Mycobacterium tuberculosis (Mtb) and Listeria monocytogenes Lm. In Batf2-deficient mice (Batf2−/−), infected with Mtb or Lm, mice survived and displayed reduced tissue pathology compared to infected control mice. Indeed, pulmonary inflammatory macrophage recruitment, pro-inflammatory cytokines and immune effectors were also decreased during tuberculosis. This explains that batf2 mRNA predictive early biomarker found in active TB patients is increased in peripheral blood. Similarly, Lm infection in human macrophages and mouse spleen and liver also increased Batf2 expression. In striking contrast, Type 2-controlled schistosomiasis exacerbates during infected Batf2−/− mice with increased intestinal fibro-granulomatous inflammation, pro-fibrotic immune cells, and elevated cytokine production leading to wasting disease and early death. Together, these data strongly indicate that Batf2 differentially regulates Type 1 and Type 2 immunity in infectious diseases.

Granisetron protects polymicrobial sepsis-induced acute lung injury in mice

Sepsis is a serious condition with a high mortality rate worldwide. Granisetron is an anti-nausea drug for patients undergoing chemotherapy. Here we aimed to identify the novel effect of granisetron on sepsis-induced acute lung injury (ALI). Our results showed that mice treated with granisetron displayed less severe lung damage than controls. Granisetron administration reduced pulmonary neutrophil recruitment after CLP. Moreover, the expressions of Cxcl1 and Cxcl2 were diminished in the presence of granisetron in THP-1 macrophages after lipopolysaccharide exposure. Additionally, granisetron could inhibit the activation of p38 MAPK and NLRP3 inflammasome both in vivo and in vitro. Collectively, granisetron protects against sepsis-induced ALI by suppressing macrophage Cxcl1/Cxcl2 expression and neutrophil recruitment in the lung.