CD5L induces inflammation and survival in RA-FLS through ERK1/2 MAPK pathway.

OBJECTIVE: To explore the effect of CD5-like molecule (CD5L) on rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) and the relative molecular mechanism of CD5L in it. METHODS: Recombinant protein CD5L was used to stimulate the cultured RA-FLS cells. The inflammation-related cytokines were determined by real time-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The signal molecules and apoptosis-related molecules were detected by western blot assay (WB), and cell counting kit-8 (CCK-8) was used to detect the proliferation. RESULTS: CD5L can increase the production of IL-6, IL-8, and TNF-α and this effect can be inhibited by signal pathway inhibitor. At the same time, CD5L activated ERK1/2 MAPK signal, inhibitor treatment can weaken the intensity of phosphorylation. In addition, CD5L can enhance the proliferation ability of RA-FLS. CONCLUSION: CD5L induces the production of inflammatory cytokines in RA-FLS through the ERK1/2 MAPK pathway and increases cell survival.

Bone morphogenetic protein 9 is a candidate prognostic biomarker and host-directed therapy target for sepsis.

Defining next-generation immune therapeutics for the treatment of sepsis will involve biomarker-based therapeutic decision-making. Bone morphogenetic protein 9 (BMP9) is a cytokine in the transforming growth factor-ß superfamily. Here, circulating BMP9 concentrations were quantified in two independent cohorts of patients with sepsis. Decreased concentrations of serum BMP9 were observed in the patients with sepsis at the time of admission as compared with healthy controls. Concentrations of BMP9 at the time of admission were also associated with 28-day mortality, because patients with sepsis at a higher risk of death had lower BMP9 concentrations. The mechanism driving the contribution of BMP9 to host immunity was further investigated using in vivo murine sepsis models and in vitro cell models. We found that BMP9 treatment improved outcome in mice with experimental sepsis. BMP9-treated mice exhibited increased macrophage influx into the peritoneal cavity and more efficient bacterial clearance than untreated mice. In vitro, BMP9 promoted macrophage recruitment, phagocytosis, and subsequent bacterial killing. We further found that deletion of the type 1 BMP receptor ALK1 in macrophages abolished BMP9-mediated protection against polymicrobial sepsis in vivo. Further experiments indicated that the regulation of macrophage activation by the BMP9-ALK1 axis was mainly mediated through the suppressor of mother against decapentaplegic 1/5 signaling pathway. Together, these results suggest that BMP9 can both serve as a biomarker for patient stratification with an independent prognostic value and be developed as a host-directed therapy for sepsis.

Elevated serum level of progranulin is associated with increased mortality in critically ill patients with candidemia.

Candidemia is a severe disease with high mortality in both intensive care unit (ICU) and non-ICU settings. Considering that progranulin (PGRN) is a potential therapeutic target for the candidemia caused by Candida albicans, we determined the serum level of PGRN after candidemia and evaluated its association with mortality. A retrospective discovery cohort (62 patients) and a validation cohort (70 patients) were enrolled. Blood was collected on day of first blood culture positivity for C. albicans, and serum PGRN levels were then measured. In the discovery cohort, all serum PGRN studied were expressed at higher levels in candidemia patients than in bacteremia patients and healthy volunteers, non-survivors presented with significantly higher serum PGRN concentrations when compared with survivors. Serum PGRN concentration was associated with 30-day mortality and patients at a higher risk of death showed higher serum PGRN levels. These results were confirmed in the independent validation cohort. Interestingly, in vitro study demonstrated that macrophages, neutrophils and lymphocytes may be the major source of PGRN production after C. albicans infection instead of epithelial cells. Our findings highlight that serum PGRN appears as a biomarker in candidemia patients and as a promising tool for mortality risk stratification in managing candidemia.

Absence of toll-like receptor 7 ameliorates survival and reduces intestinal injury in mice after Clostridium difficile infection.

Clostridioides difficile (CD) is a major cause of antibiotic-associated diarrhea and pseudomembranous enteritis. C. difficile infection (CDI) is increasingly present in the community and represents a significant burden on the healthcare system. Identification of novel immune-based therapeutic targets from a better understanding of their molecular pathogenesis is urgently required. Toll-like receptor 7 (TLR7) is an important pattern recognition receptor and function as an immune sensor that can trigger host defenses against pathogens, but the relationship between TLR7 and CDI remains unknown. Here, we reported that the expression levels of TLR7 increased significantly in patients and mice with CDI. Absence of TLR7 in mice with CDI demonstrated enhanced bacterial clearance of intestinal contents and reduced intestinal inflammation, edema, injury and prolonged the survival. TLR7 loss decreased the concentrations of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IFN-α1 in the intestine and improved tissue damage and inflammation. Flow cytometry and immunofluorescence results indicated that TLR7 enhanced leukocyte recruitment in the infected intestine. In-vitro results have shown that TLR7 impairs the phagocytosis and killing ability of macrophages to CD, prompts reactive oxygen species (ROS) production and accelerates apoptosis. To our knowledge, our study first identified TLR7 as a critical factor that contributes to the immunopathology of CDI, suggesting that targeting TLR7 might serve as a potential treatment for CDI.

Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis.

To explore the serum levels of IL-39, CXCL14, and IL-19 in patients with tuberculosis (TB) along with their clinical significances and their concentration changes in macrophages after Bacille Calmette-Guérin vaccine (BCG) or Mycobacterium tuberculosis (M. tb) H37Rv stimulation in vitro. The serum levels of IL-39, CXCL14, and IL-19 of 38 TB patients, and 20 healthy staff members were measured by enzyme-linked immunosorbent assay. Moreover, the levels of IL-19, CXCL14, and IL-39 in cultured THP-1 macrophages were detected at 12, 24, and 48 h after stimulation with BCG or M. tb H37Rv strains. It was found the serum level of IL-39 was significantly reduced and CXCL14 was remarkably elevated in TB patients. In vitro, at 48 h after stimulation, IL-39 level of cultured THP-1 macrophages in the H37Rv group was significantly lower than that in the BCG and control groups, and the CXCL14 level of cultured THP-1 macrophages in the H37Rv stimulation group was remarkably higher than that in the control group. Therefore, IL-39 and CXCL14 may be involved the pathogenesis of TB, and serum IL-39 and CXCL14 could potentially serve as a new biomarker of TB.

Study subnetwork developing pattern of autism children by non-negative matrix factorization.

BACKGROUND: As a developmental disorder, the brain networks of autism children show abnormal patterns compared with that of typically developing. The differences between them are not stable due to the developing progress of children. It has become a choice to study the differences of developing trajectories between autistic and typically developing children by investigating the change of each group respectively. Related researches studied the developing of brain network by analyzing the relationship between network indices of the entire or sub brain networks and the cognitive developing scores. METHODS: As a matrix decomposition algorithm, non-negative matrix factorization (NMF) was applied to decompose the association matrices of brain networks. By NMF, we can obtain subnetworks in an unsupervised way. The association matrices of autism and control children were estimated by their magnetoencephalography data. NMF was applied to decompose the matrices to obtain common subnetworks of both groups. Then we calculated the expression of each subnetwork in each child's brain network by two indices, energy and entropy. The relationship between the expression and the cognitive and development indices were investigated. RESULTS: We found a subnetwork with left lateralization pattern in α band showed different expression tendency in two groups. The expression indices of two groups were correlated with cognitive indices in autism and control group in an opposite way. In γ band, a subnetwork with strong connections on right hemisphere of brain showed a negative correlation between the expression indices and development indices in autism group. CONCLUSION: NMF algorithm can effectively decompose brain network to meaningful subnetworks. The finding of α band subnetworks confirms the results of abnormal lateralization of autistic children mentioned in relevant studies. We assume the results of decrease of expression of the subnetwork may relate to the dysfunction of mirror neuron. The decrease expression of γ subnetwork of autism may be related to the weaken process of high-frequency neurons in the neurotrophic competition.

The Role of Anti-Factor Xa Activity in the Management of Ecchymosis in Patients Receiving Rivaroxaban after Total Knee Arthroplasty.

This study aims to evaluate the efficacy of anti-factor Xa activity (aFXa) in predicting ecchymosis after total knee arthroplasty (TKA). One hundred and two unilateral primary TKA patients were recruited consecutively in this prospective observational study. Participants received rivaroxaban (10 mg p.o. qd) from postoperative day 1 (POD1) to POD35 and were divided into a non-ecchymosis group (group A) and an ecchymosis group (group B). AFXa was assessed as the primary outcome on POD1 and POD3. Prothrombin time (PT), activated partial thromboplastin time (APTT) and thromboelastography (TEG) were recorded both preoperatively and postoperatively (on POD1 and POD3). Other outcomes, including venous thromboembolism (VTE), blood loss and wound complications were also collected and compared. As a result, 27.5% of the participants (n = 28) were allocated into group B. Demographic data were comparable between the two groups. The aFXa levels in group B were significantly higher than those in group A on POD1 and POD3, and the aFXa level was assessed as an independent risk factor for ecchymosis. The cut-off value of aFXa was determined to be 121.38 ng/mL at maximal Youden index, associated with area under the receiver operating characteristics curve of 0.67. Group B experienced significantly more blood loss and wound complications than group A. No statistical difference was detected regarding PT, APTT and TEG parameters. AFXa is a promising parameter to predict ecchymosis after TKA. Patients with aFXa > 121.38 ng/mL should be considered as high-risk population for postoperative ecchymosis and may require intense monitoring or dosage modification of anticoagulants.

The comprehensive role of apoptosis inhibitor of macrophage (AIM) in pathological conditions.

CD5L/AIM (apoptosis inhibitor of macrophage), as an important component in maintaining tissue homeostasis and inflammation, is mainly produced and secreted by macrophages but partially dissociated and released from blood AIM-IgM. AIM plays a regulatory role in intracellular physiological mechanisms, including lipid metabolism and apoptosis. AIM not only increases in autoimmune diseases, directly targets liver cells in liver cancer and promotes cell clearance in acute kidney injury, but also causes arteriosclerosis and cardiovascular events, and aggravates inflammatory reactions in lung diseases and sepsis. Obviously, AIM plays a pleiotropic role in the body. However, to date, studies have failed to decipher the mechanisms behind its different roles (beneficial or harmful) in inflammatory regulation. The inflammatory response is a "double-edged sword," and maintaining balance is critical for effective host defense while minimizing the adverse side effects of acute inflammation. Enhancing the understanding of AIM function could provide the theoretical basis for new therapies in these pathological settings. In this review, we discuss recent studies on the roles of AIM in lipid metabolism, autoimmune diseases and organic tissues, such as liver cancer, myocardial infarction, and kidney disease.

Progranulin aggravates lethal Candida albicans sepsis by regulating inflammatory response and antifungal immunity.

Candida albicans is the most frequent pathogen of fungal sepsis associated with substantial mortality in critically ill patients and those who are immunocompromised. Identification of novel immune-based therapeutic targets from a better understanding of its molecular pathogenesis is required. Here, we reported that the production of progranulin (PGRN) levels was significantly increased in mice after invasive C.albicans infection. Mice that lacked PGRN exhibited attenuated kidney injury and increased survival upon a lethal systemic infection with C. albicans. In mice, PGRN deficiency protected against systemic candidiasis by decreasing aberrant inflammatory reactions that led to renal immune cell apoptosis and kidney injury, and by enhancing antifungal capacity of macrophages and neutrophils that limited fungal burden in the kidneys. PGRN in hematopoietic cell compartment was important for this effect. Moreover, anti-PGRN antibody treatment limited renal inflammation and fungal burden and prolonged survival after invasive C. albicans infection. In vitro, PGRN loss increased phagocytosis, phagosome formation, reactive oxygen species production, neutrophil extracellular traps release, and killing activity in macrophages or neutrophils. Mechanistic studies demonstrated that PGRN loss up-regulated Dectin-2 expression, and enhanced spleen tyrosine kinase phosphorylation and extracellular signal-regulated kinase activation in macrophages and neutrophils. In summary, we identified PGRN as a critical factor that contributes to the immunopathology of invasive C.albicans infection, suggesting that targeting PGRN might serve as a novel treatment for fungal infection.

CXCL14 Protects against Polymicrobial Sepsis by Enhancing Antibacterial Functions of Macrophages.

Rapid and effective control of bacterial infection is critical for the treatment of bacterial sepsis. CXCL14 (CXC motif ligand 14) is an important chemokine involved in infection and immunity, which can bind to CXCR4. However, the contribution of the CXCL14/CXCR4 chemokine axis to bacterial clearance in sepsis remains unknown. Here, the impact of CXCL14/CXCR4 blockade or CXCL14 administration on sepsis was assessed using murine and cell models, as well as human samples. CXCL14 protein concentrations were elevated in mice after cecal ligation and puncture (CLP)-induced sepsis. In vivo, CXCL14 blockade using anti-CXCL14 antibody or CXCL14 knockdown by adeno-associated virus carrying-CXCL14 shRNA significantly increased mortality and bacterial burden, which was paralleled by significantly decreased macrophage influx and M2 macrophage polarization at the site of infection after CLP. Therapeutic administration of CXCL14 improved mortality and bacterial clearance after CLP in a CXCR4-dependent manner, and macrophages, but not neutrophils, were important for the protective effect of CXCL14 in sepsis. In vitro, CXCL14 directly enhanced bacterial phagocytosis and killing of macrophages, and it also increased phagosome formation and reactive oxygen species production in macrophages. Furthermore, inhibiting the activation of PI3K/Akt and NF-κB signaling pathways, but not STAT1 (signal transducer and activator of transcription 1), abrogated the enhanced antibacterial effects of CXCL14 on macrophages. Finally, circulating CXCL14 concentrations were significantly upregulated in patients with sepsis. CXCL14 could enhance bacterial phagocytosis and killing in human monocyte-derived macrophages, which was dependent on CXCR4. Therefore, our results indicate a previously undescribed role of the CXCL14/CXCR4 axis and suggest CXCL14 as a potential adjunct therapy in bacterial sepsis.

Elevated serum level of human epididymal protein 4 (HE4) predicts poor prognosis in the critically ill with sepsis: A prospective observational cohort study.

OBJECTIVE: Human epididymal protein 4 (HE4) has been widely used as an important clinical tumor biomarker for epithelial ovarian cancer. HE4 has recently been suggested to be an inflammatory biomarker and we hypothesized that the serum HE4 level upon intensive care unit (ICU) admission might predict prognosis in septic patients. We hypothesized that serum HE4 level upon intensive care unit (ICU) admission could predict prognosis in septic patients. METHODS: Serum levels of HE4, procalcitonin (PCT), C-reactive protein (CRP), IL-6 and IL-8 were quantified, and sequential organ failure assessment (SOFA) scores were recorded on day one of admission to ICU. The area under the receiver operating characteristic (ROC) curve (AUC) analysis of HE4, IL-6, PCT and SOFA at ICU admission for 28-day mortality was used to evaluate the ability of HE4 in predicting 28-day mortality of sepsis. Multivariate regression analysis was used to identify the independent risk factors for 28-day mortality. RESULTS: A total of 1289 patients were recruited, and 117 patients were included for final analysis. On day of ICU admission, septic patients had significantly higher levels of serum HE4 than those with infection without sepsis, those with ovarian cancer, or healthy controls. Compared with septic survivors, septic non-survivors presented with significantly higher serum HE4 concentrations. Serum levels of HE4 correlated with disease severity scores and cytokine levels (IL-6 and IL-8). Upon ICU admission, the AUC for HE4 level association with 28-day mortality was 0.881, higher than the AUC for SOFA (0.713), IL-6 (0.589), and PCT (0.567). A regression analysis showed that HE4 was an independent mortality predictor. CONCLUSION: HE4 can predict poor prognosis in septic patients, which may help to identify a group of septic patients at high risk of death.

[Asymmetric response mechanism of auditory event related potentials].

The classical auditory oddball paradigm is a commonly used experimental paradigm for evoking event related potentials (ERPs). The present study was aimed to explore the auditory cognitive processing mechanism of space perception of human brain. We employed an auditory oddball paradigm of binaural unbiased and biased sound intensity to compare and analyze the response characteristics of ERP. By focusing on the spatial lateralization characteristics of P300 and mismatch negativity (MMN) components, we analyzed their lateralization trends according to the laterality index. We found that both P300 and MMN components showed right-hemisphere lateralization phenomenon under the stimulation of asymmetric intensity of auditory acoustic. The results suggested that the right hemisphere of human brain played a key role in spatial information processing. The results also indicated that the hemispherical characteristics of the brain were not related to the actual spatial direction of the auditory stimulus, but were determined by the hemispherical functions of the brain. Furthermore, the results suggested that the MMN components induced by spatial differences were stronger in females than those in males.

Il-34 regulates MAPKs, PI3K/Akt, JAK and NF-κB pathways and induces the expression of inflammatory factors in RA-FLS.

OBJECTIVES: To explore the role of interleukin 34 (IL-34) in rheumatoid arthritis (RA) and its related signalling pathways as well as the expression levels of IL-34 in collagen-induced arthritis (CIA) modelling mice. METHODS: Recombination IL-34 was used to stimulate cultured RA fibroblast-like synoviocytes (RA-FLS). The expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA), and the levels of phosphorylation signalling molecules were detected by western blotting assay (WB). After the establishment of the CIA model, paw indexes and serum IL-34 expression levels of mice were evaluated. RESULTS: IL-34 significantly increased the secretion of IL-8 and TNF-α but had no significant effect on IL-6, and this effect could be impaired by signal inhibitors. At the same time, IL-34 activated multiple signalling pathways, whereas treating with inhibitors could reduce phosphorylation intensity. In animal experiments, mice in the model group had lost weight, and their paws were obviously swollen, ulcerous, and even stiffened. The hyperplasia of synovial tissue, infiltration of many inflammatory cells, and destruction of bone and cartilage from the typical pannus formation were also apparently observed. CONCLUSIONS: IL-34 can mediate the production and secretion of IL-8 and TNF-α in RA-FLS cells through MAPKs, PI3K/Akt, JAK and NF-κB signalling pathways, while the expression of serum IL-34 in collagen-induced arthritis mice is also upregulated.

Analysis of serum hepatitis B virus RNA levels among HBsAg and HBsAb copositive patients and its correlation with HBV DNA.

ABSTRACT: There are approximately 2 billion HBV-infected individuals worldwide, and approximately 1.87% to 7% of these individuals are copositive for HBsAg and HBsAb.Our study detected hepatitis B virus pgRNA (HBV RNA) levels in HBsAg and HBsAb copositive patients and then analyzed the correlation with HBV DNA, HBsAg, ALT, and AST levels. A total of 149 HBsAg and HBsAb copositive patients were identified from 66,617 outpatients.HBV RNA, HBV DNA, HBsAg, ALT, and AST serum levels were significantly different in different natural phases of HBV infection (immune tolerance phase, immune clearance phase, low replication phase, and reactivation phase) with statistical significance (P < .01). HBV RNA levels were positively correlated with HBV DNA, HBsAg, ALT, and AST levels. HBV RNA and HBV DNA levels were significantly increased in the HBeAg-positive group (66 patients) compared with the HBeAg-negative group (83 patients) (P < .01). In the HBeAg-positive group, HBV RNA levels were positively correlated with HBV DNA and HBsAg levels. In the HBeAg-negative group, HBV RNA levels were positively correlated with HBV DNA. Serum HBV RNA levels were positively correlated with HBV DNA, HBsAg, ALT, and AST levels.HBV RNA could be used as a virological indicator for antiviral therapy in HBsAg and HBsAb copositive hepatitis B patients.

Serum CD5L predicts acute lung parenchymal injury and acute respiratory distress syndrome in trauma patients.

ABSTRACT: Cluster of differentiation 5 antigen-like (CD5L), derived from alveolar epithelial cells partly, is a secreted protein. It is shown that CD5L is associated with lung inflammation and systemic inflammatory diseases, but the relationship between CD5L and trauma-related acute lung parenchymal injury (PLI), acute lung injury or acute respiratory distress syndrome (ARDS) is unclear. This study aims to explore the value of serum CD5L levels in predicting trauma-associated PLI/ARDS and its potential clinical significance.This is a prospective observational study, and a total of 127 trauma patients were recruited from the emergency department (ED), and among them, 81 suffered from PLI/ARDS within 24 hours after trauma, and 46 suffered from trauma without PLI/ARDS. Fifty healthy subjects from the medical examination center were also recruited as controls for comparison. The serum CD5L level was measured within 24 hours of admission. The receiver operating characteristic analysis and logistic regression analysis were used to identify the correlation between high CD5L and trauma associated-PLI/ARDS within 24 hours following trauma.The trauma associated-PLI/ARDS subjects showed a significantly higher level of serum CD5L on emergency department admission within 24 hours after trauma compared with its level in non-trauma associated-PLI/ARDS subjects and healthy subjects. The initial CD5L concentration higher than 150.3 ng/mL was identified as indicating a high risk of PLI/ARDS within 24 hours following trauma (95% confidence interval: 0.674-0.878; P < .001). Moreover, CD5L was an independent risk factor for trauma associated-PLI/ARDS within 24 hours following trauma.CD5L could predict PLI/ARDS within 24 hours following trauma.

Apoptosis inhibitor of macrophage/CD5L is associated with disease activity in rheumatoid arthritis.

OBJECTIVES: To investigate the association between apoptosis inhibitor of macrophage (AIM) and disease activity in patients with rheumatoid arthritis (RA). METHODS: In this study, concentrations of serum AIM in 110 RA patients, 38 patients with osteoarthritis (OA) and 50 sex- and age-matched control subjects were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum AIM concentrations in RA patients were dramatically higher than those from patients with OA or healthy controls. The levels of synovial fluid AIM displayed a significant increase as compared with OA patients. More importantly, AIM levels were significantly correlated with RA disease activity features such as ESR, CRP and DAS28. The predictive value of AIM on high disease activity was superior to those of CRP and ESR. A noteworthy correlation in our study was observed between the serum AIM levels and laboratory parameters, particularly serum lipids. Furthermore, serum AIM levels could be significantly down-regulated after effective integrative treatment. CONCLUSIONS: AIM may serve as a novel sensitive biomarker to assist disease activity assessment and monitor therapeutic effects in active RA patients.

Risk of Clostridium tetani infection in an elderly patient following hemorrhoid ligation.

Tetanus after gastrointestinal surgery is an extremely rare but very dangerous disease caused by infection with Clostridium tetani. Tetanus can occur due to bacterial infection during surgery or dressing change, or the bacteria may exist in the patient's intestines and be discharged with feces. This report describes a 71-year-old woman who developed tetanus 3 days after a hemorrhoidal ligation. Clinicians need to be aware of symptoms of C. tetani infection that might present in patients who have undergone gastrointestinal procedures.

Interleukin-26 is overexpressed in human sepsis and contributes to inflammation, organ injury, and mortality in murine sepsis.

BACKGROUND: Sepsis is a serious syndrome that is caused by an unbalanced host inflammatory response to an infection. The cytokine network plays a pivotal role in the orchestration of inflammatory response during sepsis. IL-26 is an emerging proinflammatory member of the IL-10 cytokine family with multifaceted actions in inflammatory disorders. However, its role in the pathogenesis of sepsis remains unknown. METHODS: Serum IL-26 level was measured and analyzed in 52 septic patients sampled on the day of intensive care unit (ICU) admission, 18 non-septic ICU patient controls, and 30 healthy volunteers. In addition, the effects of recombinant human IL-26 on host inflammatory response in cecal ligation and puncture (CLP)-induced polymicrobial sepsis were determined. RESULTS: On the day of ICU admission, the patients with sepsis showed a significant increase in serum IL-26 levels compared with ICU patient controls and healthy volunteers, and the serum IL-26 levels were related to the severity of sepsis. Nonsurvivors of septic patients displayed significantly higher serum IL-26 levels compared with survivors. A high serum IL-26 level on ICU admission was associated with 28-day mortality, and IL-26 was found to be an independent predictor of 28-day mortality in septic patients by logistic regression analysis. Furthermore, administration of recombinant human IL-26 increased lethality in CLP-induced polymicrobial sepsis. Despite a lower bacterial load, septic mice treated with recombinant IL-26 had higher concentrations of IL-1ß, IL-4, IL-6, IL-10, IL-17A, TNF-α, CXCL1, and CCL2 in peritoneal lavage fluid and blood and demonstrated more severe multiple organ injury (including lung, liver and kidney) as indicated by clinical chemistry and histopathology. Furthermore, septic mice treated with recombinant human IL-26 showed an increased neutrophil recruitment to the peritoneal cavity. CONCLUSIONS: Septic patients had elevated serum IL-26 levels, which may correlate with disease severity and mortality. In experimental sepsis, we demonstrated a previously unrecognized role of IL-26 in increasing lethality despite promoting antibacterial host responses.