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Changes in cytokine production are known to contribute to the pathogenesis of sickle-cell disease (SCD), particularly in painful acute complications (crises) and episodes of post-transfusion hemolysis. Little is known about cytokine profiles in patients with these complications. We investigated possible associations between cytokine profile and the onset of delayed hemolytic transfusion reactions (DHTRs), particularly during acute-phase episodes, to improve characterization of the biological parameters predictive of such events. We included SCD patients with severe acute symptoms (n = 36) or steady-state disease (n = 31), both possibly leading to a DHTR (n = 18) event. Luminex® technology was used to determine the plasma concentrations of 23 cytokines. Regardless of clinical context, the concentrations of interleukin (IL)-6, IL-10, inducible protein-10, and macrophage inflammatory protein-1β were higher in plasma samples from SCD patients than in those from healthy controls. IL-6 and IL-10 concentrations were even higher in acute-phase plasma samples from SCD patients. In addition, IL-27 and TNFα levels were higher, and IL-6 and RANTES levels were lower in acute-phase SCD patients just before the onset of DHTR than in patients experiencing painful occlusive episodes. In addition to reporting the plasma cytokine profiles of SCD patients in various clinical phases of the disease, we provide the first evidence of a significant association between low plasma TNFα concentration, high plasma IP-10 concentration and the onset of DHTR in SCD patients. Show less

Clinical and experimental studies have established that immune cells such as alternatively activated (M2) macrophages and Th17 cells play a role in the progression of chronic kidney disease, but the endogenous pathways that limit these processes are not well understood. The cytokine IL-27 has been shown to limit immune-mediated pathology in other systems by effects on these cell types, but this has not been thoroughly investigated in the kidney. Unilateral ureteral obstruction was performed on wild-type and IL-27Rα Show less

The major cause behind lung cancer development is exposure to various polycyclic aromatic hydrocarbons like benzo(a)pyrene (BaP) present in tobacco smoke, motor vehicle, and industrial exhaust. BaP is reported to induce the expression of various pro-inflammatory cytokines and matrix remodeling proteins. It is also responsible for dysfunction and exhaustion of the killing capacity of CD8+ T lymphocytes, one of the important components of the immune system which can kill tumor cells. We tried to evaluate the synergistic role of IL-27 and IL-28B in modulation of BaP-induced lung carcinogenesis associated with various hallmarks like pulmonary redox imbalance, angiogenesis, inflammation and cell proliferation in lung tissue. BaP was treated to Swiss albino mice to develop lung tumor. After the confirmation of lung tumor development Swiss albino mice were treated with IL-27 and IL-28B alone or in combination intraperitoneally. Histological analysis, immunohistochemistry, biochemical assay, western blot analysis, cell cytotoxicity assay, real-time PCR assay etc. were performed to evaluate the modulatory role of IL-27 and IL-28B. We observed that IL-27 and IL-28B were able to suppress the expression of lung cancer-associated NFkB, COX-2, and iNOS. The expression of TNF-α, PCNA and some matrix remodeling enzymes were also modulated upon IL-27 and IL-28B treatment. Although the population of lung residing CD8+ T cells in tumor bearing lung tissue were unresponsive but the activity of systemic CD8+ cells was increased. Results hinted that IL-27 along with IL-28B were able to ameliorate various hallmarks ranging from angiogenesis to inflammation associated with the BaP-induced lung carcinogenesis. From this study, we propose that IL-27 and IL28B can be used as immunotherapeutic agent to regulate lung cancer. Show less

Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease. Show less

SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis in animal models and clinical trials. In this report, we show that aspiration of the GU-rich ssRNA oligonucleotide ORN06 into mouse lungs induces all of the above COVID-19-like symptoms. Men tend to have more severe COVID-19 symptoms than women, and in the aspirated ORN06 model, male mice tended to have more severe symptoms than female mice. Intraperitoneal injections of SAP starting from day 1 post ORN06 aspiration attenuated the ORN06-induced increase in the number of inflammatory cells and formation of clot-like aggregates in the mouse lung fluid, reduced ORN06-increased alveolar wall thickness and accumulation of exudates in the alveolar airspace, and attenuated an ORN06-induced upregulation of the inflammatory cytokines IL-1β, IL-6, IL-12p70, IL-23, and IL-27 in serum. Together, these results suggest that aspiration of ORN06 is a simple model for both COVID-19 as well as cytokine storm in general, and that SAP is a potential therapeutic for diseases with COVID-19-like symptoms as well as diseases that generate a cytokine storm. Show less

Heterozygous gain-of-function (GOF) mutations in STAT1 in patients with chronic mucocutaneous candidiasis (CMC) and hypothyroidism were discovered in 2011. CMC is the recurrent or persistent mucocutaneous infection by Candida fungi, and hypothyroidism results from autoimmune thyroiditis. Patients with these diseases develop other infectious diseases, including viral, bacterial, and fungal diseases, and other autoimmune manifestations, including enterocolitis, immune cytopenia, endocrinopathies, and systemic lupus erythematosus. STAT1-GOF mutations are highly penetrant with a median age at onset of 1 year and often underlie an autosomal dominant trait. As many as 105 mutations at 72 residues, including 65 recurrent mutations, have already been reported in more than 400 patients worldwide. The GOF mechanism involves impaired dephosphorylation of STAT1 in the nucleus. Patient cells show enhanced STAT1-dependent responses to type I and II interferons (IFNs) and IL-27. This impairs Th17 cell development, which accounts for CMC. The pathogenesis of autoimmunity likely involves enhanced type I IFN responses, as in other type I interferonopathies. The pathogenesis of other infections, especially those caused by intramacrophagic bacteria and fungi, which are otherwise seen in patients with diminished type II IFN immunity, has remained mysterious. The cumulative survival rates of patients with and without severe disease (invasive infection, cancer, and/or symptomatic aneurysm) at 60 years of age are 31% and 87%, respectively. Severe autoimmunity also worsens the prognosis. The treatment of patients with STAT1-GOF mutations who suffer from severe infectious and autoimmune manifestations relies on hematopoietic stem cell transplantation and/or oral JAK inhibitors. Show less

Several studies have suggested that chemokine receptors are important mediators of inflammatory response in rheumatoid arthritis (RA). B cells are also known to play an important role in RA pathology. C-X-C chemokine receptor type 3 (CXCR3) is considered a potential therapeutic target in different inflammatory diseases; however, the mechanism remains unclear. Here, we evaluated the potentially protective effect of AMG487, a selective CXCR3 antagonist, in collagen-induced arthritis (CIA) mouse model. CIA mice were treated with AMG487 (5 mg/kg) every 48 h, from day 21 until day 41. We then investigated the effect of AMG487 on NF-κB p65-, NOS2-, MCP-1-, TNF-α-, IFN-γ, IL-4-, and IL-27-producing CD19 Show less

IL-27 is a cytokine that exerts diverse effects on the cells of innate and adaptive immune systems. Chiefly expressed in macrophages and dendritic cells during the early phase of Leishmania infection, IL-27 contributes to the protection against L. major infection but suppresses the protective Th1 response against L. donovani, L. infantum, L. amazonensis and L. braziliensis infections, suggesting its functional duality. During the late stage of Leishmania infection, IL-27 limits the immunopathogenic reactions and tissue damages. Herein, we analyze the mechanism of the functional duality of IL-27 in the resistance or susceptibility to Leishmania infection, prompting IL-27 for anti-Leishmanial therapy. Show less

The interleukin 12 (IL-12) family of cytokines regulates T cell functions and is key for the orchestration of immune responses. Each heterodimeric IL-12 family member is a glycoprotein. However, the impact of glycosylation on biogenesis and function of the different family members has remained incompletely defined. Here, we identify glycosylation sites within human IL-12 family subunits that become modified upon secretion. Building on these insights, we show that glycosylation is dispensable for secretion of human IL-12 family cytokines except for IL-35. Furthermore, our data show that glycosylation differentially influences IL-12 family cytokine functionality, with IL-27 being most strongly affected. Taken together, our study provides a comprehensive analysis of how glycosylation affects biogenesis and function of a key human cytokine family and provides the basis for selectively modulating their secretion via targeting glycosylation. Show less

Epstein-Barr virus-induced gene 3 (EBI3) is a subunit common to IL-27, IL-35, and IL-39. Here, we explore an intracellular role of EBI3 that is independent of its function in cytokines. EBI3-deficient naive CD4+ T cells had reduced IFN-γ production and failed to induce T cell-dependent colitis in mice. Similarly reduced IFN-γ production was observed in vitro in EBI3-deficient CD4+ T cells differentiated under pathogenic Th17 polarizing conditions with IL-23. This is because the induction of expression of one of the IL-23 receptor (IL-23R) subunits, IL-23Rα, but not another IL-23R subunit, IL-12Rβ1, was selectively decreased at the protein level, but not the mRNA level. EBI3 augmented IL-23Rα expression via binding to the chaperone molecule calnexin and to IL-23Rα in a peptide-dependent manner, but not a glycan-dependent manner. Indeed, EBI3 failed to augment IL-23Rα expression in the absence of endogenous calnexin. Moreover, EBI3 poorly augmented the expression of G149R, an IL-23Rα variant that protects against the development of human colitis, because binding of EBI3 to the variant was reduced. Taken together with the result that EBI3 expression is inducible in T cells, the present results suggest that EBI3 plays a critical role in augmenting IL-23Rα protein expression via calnexin under inflammatory conditions. Show less

IL-27 is a pleiotropic cytokine capable of influencing both innate and adaptive immune responses. With anti- and pro-inflammatory activity, IL-27 exerts its opposing effects in a cell-dependent and infectious context-specific manner. Upon pathogenic stimuli, IL-27 regulates innate immune cells, such as monocytes, dendritic cells, macrophages and neutrophils. Immune responses involving these innate cells that are negatively regulated by IL-27 signaling include inflammatory cytokine production, phagolysosomal acidification following phagocytosis, oxidative burst and autophagy. IL-27 signaling is crucial in maintaining the subtle balance between Th1 and Th2 immunity, in which protective inflammation is upregulated within the early stages of infection and subsequently downregulated once microbial growth is controlled. The immunomodulatory effects of IL-27 provide promising therapeutic targets for multiple disease types. Show less

To establish a secondary hemophagocytic lymphohistiocytosis(HLH) mouse model, and to investigate the effect of ruxolitinib on the disease manifestation of model mice. Wild type C57BL/6 mice were randomly divided into 4 groups: two groups of mice were intraperitoneally injected with CpG oligodeoxynucleotide 1826 (CpG-ODN1826) every other day to induce HLH, and other two groups were control groups. One group of the CpG-ODN1826 groups and one of the control groups were given ruxolitinib, and other two groups were given the same amount of PBS. Blood samples, serum ferritin and hepatic/spleen weights of experimental mice were detected and serum cytokine levels were measured by ELISA. Compared with the control groups, the levels of white blood cells, hemoglobin and platelets in the CpG-ODN1826 groups were significantly lower (P＜0.05); and liver/body weight, spleen/body weight, serum ferritin, sCD25, IL-10, IL-1β, IFN-Ƴ, IL-12p70, GM-CSF, TNF-α and IL-18 levels significantly increased (P＜0.05). There was no significant difference in the levels of IL-2, IL-4, IL-5, IL-6, IL-22, IL-13, IL-27 and IL-23 between the two groups (P＞0.05). The spleen in CpG group had disordered internal structure, expanding red pulp and hyperplastic nucleated cells. The liver had severe perivascular inflammations. The spleen/weight of the ruxolitinib-treated mice in the CpG-ODN1826 group was significantly smaller than that of the unapplied ruxolitinib (P＜0.05). The CpG-ODN1826 can induce secondary HLH symptoms in wild type C57BL/6 mice. Ruxolitinib can alleviate the symptoms of splenomegaly in HLH model mice. Show less

In the last few years, a new actor hit the scene of the tumor microenvironment, the p28 subunit of interleukin (IL)-27, known as IL-30. Its molecular structure allows it to function as an autonomous cytokine and, alternatively, to pair with other subunits to form heterodimeric complexes and enables it to play different, and not fully elucidated, roles in immunity. However, data from the experimental models and clinical samples, suggest IL-30's engagement in the relationship between cancer and myeloid cells, which fosters the tumor microenvironment and the cancer stem cell niche, boosting the disease progression. Activated myeloid cells are the primary cellular source and one of the targets of IL-30, which can also be produced by cancer cells, especially, in aggressive tumors, as observed in the breast and prostate. This review briefly reports on the immunobiology of IL-30 and related cytokines, by comparing mouse and human counterparts, and then focuses on the mechanisms whereby IL-30 amplifies intratumoral myeloid cell infiltrate and triggers a vicious cycle that worsens immunosuppression in the tumor microenvironment (TME) and constitutes a real threat for a successful immunotherapeutic strategy. Show less

Toll-like receptor 4 (TLR4) contributes to the pathogenesis of coronary ischemia/reperfusion (IR). To test whether the new TLR4 antagonist, ApTOLL, may prevent coronary IR damage, we administered 0.078 mg/kg ApTOLL or Placebo in pigs subjected to IR, analyzing the levels of cardiac troponins, matrix metalloproteinases, pro-, and anti-inflammatory cytokines, heart function, and tissue integrity over a period of 7 days after IR. Our results show that ApTOLL reduced cardiac troponin-1 24 h after administration, improving heart function, as detected by a significant recovery of the left ventricle ejection fraction (LVEF) and the shortening fraction (FS) cardiac parameters. The extension of necrotic and fibrotic areas was also reduced, as detected by Evans blue/2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin/Eosine, and Masson Trichrome staining of heart sections, together with a significant reduction in the expression of the extracellular matrix-degrading, matrix metalloproteinase 9. Finally, the expression of the following cytokines, CCL1, CCL2, MIP1-A-B, CCL5, CD40L, C5/C5A, CXCL1, CXCL10, CXCL11, CXCL12, G-CSF, GM-CSF, ICAM-1, INF-g, IL1-a, ILI-b, IL-1Ra, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, IL16, IL17-A, IL17- E, IL18, IL21, IL27, IL32, MIF, SERPIN-E1, TNF-a, and TREM-1, were also assayed, detecting a pronounced decrease of pro-inflammatory cytokines after 7 days of treatment with ApTOLL. Altogether, our results show that ApTOLL is a promising new tool for the treatment of acute myocardial infarction (AMI). Show less

Tuberculosis (TB) is an infectious disease and its mortality rate ranks first. Latent tuberculosis infection (LTBI) means that a patient is infected with Mycobacterium tuberculosis, but has no relative clinical symptoms. It has been estimated that approximately 10% of patients with LTBI would develop into active tuberculosis. Therefore, it was urgent to search for more efficient biomarkers to discriminate LTBI from healthy population. The Luminex assay was employed to detect the quantity of cytokines secreted by mononuclear cells from peripheral blood stimulated with the ESAT6 protein among TB, LTBI and healthy controls. The cytokine profile was analyzed by principal components analysis and the receiver operating characteristic curve analysis. The principal components analysis indicated that LTBI and TB were clearly separated from healthy controls, and that LTBI was also successfully differentiated from healthy controls. The cytokine profiling method to distinguish LTBI from healthy controls has a sensitivity and specificity of 100%. Nine potential biomarkers, including IL-23, IL-21, HGF, Bngf, IL-27, IL-31, IL-1β, IL-22 and IL-18, were identified, and these cytokines were considered as a potential cytokine complex for more effectively discriminating LTBI from healthy controls. IL-23, IL-21, HGF, Bngf, IL-27, IL-31, IL-1β, IL-22 and IL-18 were demonstrated to be the potential cytokine complex for the assessment between LTBI and healthy controls. Show less

Obesity, a chronic low-grade inflammation metabolic abnormality, is related to high proinflammatory cytokines concentrations. Epstein-Barr virus-induced gene 3 (EBI3) encodes for the EBI3 beta subunit that constitutes interleukin (IL) 27 and 35. Our objective was to assess the association of three EBI3 single nucleotide polymorphisms (SNPs) with the presence of central obesity in a group of Mexican subjects. The rs428253, rs4740, and rs4905 EBI3 SNPs were genotyped in 1323 individuals (1092 central obese and 231 non-central obese). We also analyzed IL-6, IL-27, and IL-35 concentrations. Under different models, the rs4740 (OR = 0.384, P Show less

Recently, emerging evidence strongly suggested that the activation of interleukin-27 Receptor α (IL-27Rα) could modulate different inflammatory diseases. However, whether IL-27Rα affects allotransplantation rejection is not fully understood. Here, we investigated the role of IL-27Rα on allorejection both in vivo and in vitro. The skin allotransplantation mice models were established, and the dynamic IL-27Rα/IL-27 expression was detected, and IL-27Rα Show less

The prevalence of helminth infections exhibits an inverse association with the prevalence of Type 2 diabetes mellitus (T2DM), and helminths are postulated to mediate a protective effect against T2DM. However, the biological mechanism behind this effect is not known. We postulated that helminth infections act by modulating the pro-inflammatory cytokine and chemokine milieu that is characteristic of T2DM. To examine the association of cytokines and chemokines in helminth-diabetes co-morbidity, we measured the plasma levels of a panel of pro-inflammatory cytokines and chemokines in individuals with Strongyloides stercoralis infection (Ss+) and T2DM at the time of Ss diagnosis and then 6 months after definitive anthelmintic treatment along with uninfected control individuals with T2DM alone (Ss-). Ss+ individuals exhibited significantly diminished levels of the pro-inflammatory cytokines-IL-1α, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-27, G-CSF and GM-CSF and chemokines-CCL1, CCL2, CCL3, CCL11, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10 and CXCL11. In contrast, Ss+ individuals exhibited significantly elevated levels of IL-1Ra. Anthelmintic treatment resulted in increased levels of all of the cytokines and chemokines. Thus, helminth infections alleviate and anthelmintic therapy partially restores the plasma cytokine and chemokine levels in helminth-diabetes co-morbidity. Our data therefore offer a plausible biological mechanism for the protective effect of helminth infections against T2DM. Show less

Benign prostatic hyperplasia (BPH) is the most common urologic disease affecting aging men. The pathogenesis of BPH is multi-factorial, and chronic inflammation (CI) might be the central mechanism. Interleukin (IL)-27 signaling has been suggested as a modulator in autoimmune and inflammatory conditions. In this study, we used microarray experiments to analyze gene expression and molecular phenotypic associated with BPH progression, with a particular focus on CI and IL-27/IL-27RA signaling, and verified the microarray data in cell biology experiments. Thirty BPH patients' specimens and clinical parameters were analyzed. BPH patients were divided into two groups based on the average prostate volume (41.5 mL): group 1, ≤40 mL; and group 2, >40 mL. Microarray experiments were conducted to identify differentially expressed genes (DEGs) by applying appropriate biostatistics to normalize and analyze the dataset. The candidate gene ( Eighty-three percent of BPH specimens contained inflammatory infiltrates, and the predominant type was CI. The serum PSA levels and prevalence of CI were higher in group 2. Microarray experiments identified 361 DEGs between these 2 groups. Our study revealed that down-regulation of Show less

High serum levels of the acute phase protein C-reactive protein (CRP) are associated with an adverse prognosis in renal cancer. The acute phase reaction is cytokine-driven and includes a wide range of inflammatory mediators. This overall profile of the response depends on the inducing event and can also differ between patients. We investigated an extended acute phase cytokine profile for 97 renal cancer patients. Initial studies showed that the serum CRP levels had an expected prognostic association together with tumor size, stage, nuclear grading, and Leibovich score. Interleukin (IL)6 family cytokines, IL1 subfamily mediators, and tumor necrosis factor (TNF)α can all be drivers of the acute phase response. Initial studies suggested that serum IL33Rα (the soluble IL33 receptor α chain) levels were also associated with prognosis, although the impact of IL33Rα is dependent on the overall cytokine profile, including seven IL6 family members (IL6, IL6Rα, gp130, IL27, IL31, CNTF, and OSM), two IL1 subfamily members (IL1RA and IL33Rα), and TNFα. We identified a patient subset characterized by particularly high levels of IL6, IL33Rα, and TNFα alongside an adverse prognosis. Thus, the acute phase cytokine reaction differs between renal cancer patients, and differences in the acute phase cytokine profile are associated with prognosis. Show less

Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor. In vitro dose-dependent treatment with caffeine down-regulates mRNA levels of key inflammation-related genes in peripheral blood mononuclear cells. So far, no robust data are available about the possible contribution of caffeine in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokine serum levels. We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K). Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided into four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4). At the end of questionnaire filling, blood samples were collected from each patient to assess cytokine levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFNγ, IFNα and BLyS. We enrolled 89 consecutive SLE patients. We observed a negative correlation between caffeine consumption and disease activity, measured with SLEDAI-2K. A significantly higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementaemia and anti-dsDNA positivity was observed in patients with a low intake of caffeine. Furthermore, patients with a low intake of caffeine were more frequently treated with glucocorticoids. Regarding cytokine analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found ( In this report we demonstrated the impact of caffeine on SLE disease activity status, as confirmed by the inverse correlation between its intake and both SLEDAI-2K values and cytokine levels. Moreover, patients with a low caffeine consumption seem to have a more severe disease phenotype. Show less

To investigate the relationship between the biochemical parameters, the pulmonary pathologic injury and the immune mechanism of severe sepsis in infant porcine, and the intervention effect of Shenfu injection. Panamanian infant porcine (2-3 months old) were divided into sham operation group (Sham group; intravenous injection of normal saline), lipopolysaccharide (LPS) induced severe sepsis model group (LPS group; intravenous injection of LPS 1 mg/kg, and continuing at 0.5 mg×kg Compared with Sham group, the levels of CRP, PCT and Lac in LPS group significantly increased, and PaO The increased abnormality of BE, Lac, and PaO Show less

We have previously shown that treatment of female NOD mice with a potent nonselective histone deacetylase inhibitor attenuated experimental autoimmune encephalomyelitis, a model for progressive multiple sclerosis. Herein we show that immunization with the MOG Show less

In many infectious diseases, the immune response operates as a double-edged sword. While required for protective immunity, infection-induced inflammation can be detrimental if it is not properly controlled, causing collateral body damage and potentially leading to death. It is in this context that the potent anti-inflammatory cytokine interleukin-10 (IL-10) is required to dampen the pro-inflammatory immune response that hallmarks trypanosomosis. Effective control of this infection requires not just the action of antibodies specific for the parasite's variable surface glycoprotein (VSG) coat antigens, but also a pro-inflammatory immune response mediated mainly by IFNγ, TNF, and NO. However, strict control of inflammation is mandatory, as IL-10-deficient mice succumb from an unrestrained cytokine storm within 10 days of a Show less

Immunobiotics have emerged as a promising intervention to alleviate intestinal damage in inflammatory bowel disease (IBD). However, the beneficial properties of immunobiotics are strain dependent and, therefore, each strain has to be evaluated in order to demonstrate its potential application in IBD. Our previous Show less