Differences In IL-6 Research Articles

Proinflammatory Cytokines Profile, a Link Between Multiple Myeloma and Gaucher Disease

Gaucher disease (GD) is characterized by a latent chronic inflammatory macrophage activation expressed by an imbalance of pro-inflammatory cytokines, hyperferritinemia, hypergammaglobulinemia, altered calcium homeostasis and metabolic syndrome. The incidence of Monoclonal Gammopathy of Uncertain Significance (MGUS) and multiple myeloma (MM) is increased in GD1 patients (3.5-12.5). The hypothesis is that deregulation of immune system resulting from glucocerebroside accumulation may influence the development of hematological malignancies. However, the pathological mechanisms that influence in MM development in GD1 patients are unknown. Cytokines produced secondary to glucocerebroside accumulation, may be a critical factor to explain the pathogenesis of MM in GD. This cytokine environment could trigger lymphocyte expansion and ultimately transformation. Objective: To analyze and compare the proinflammatory cytokines profile among MGUS, MM and GD1patients.Methods: Between February-May 2014 we have analyzed a panel of eight cytokines (IL4, IL6, IL7, IL10, IL13, MIP1α, MIP1β and TNF) by Luminex®100 platform and Millipore cytokine kits. The analysis was performed in plasma samples stored at diagnosis in Aragon Biobank. We have studied four cohorts: 71 healthy controls, 38 GD1 patients (36.8% women, mean age 39.2 years, range: 17-79), 36 MGUS (58.3% women, mean age: 75 years, range 53-89), 11 IgGk; 6 IgGL; 5 IgAk; 8 IgAL; 3 IgMk; 3 doble IgG+IgA and 49 MM (42% women, mean age 68 years, range 39-89), 20 IgGk; 5 IgGL; 8 IgAk; 5 IgAL, 8 ligth chain disease and 3 doble IgG+IgA. Concerning ISS classification 44.0% MM patients had a score 1, 24.3% score 2 and 31.7% score 3. All patients with MGUS or MM had been diagnosed consecutively during 2009 and followed until now. Clinical and analytical data of MGUS and MM were obtained from the records of the Hematology Department; and the data of GD1 patients from the Spanish Registry (FEETEG). Data were analyzed using non-parametric tests (Mann-Whitney-U and Kruskall-Wallis).Results: After 5 years in follow-up 21 MM patients had died (42.8%) and 8 in the MGUS group (22.2%), 4 MGUS developed a MM (11.1%); and 8 another neoplasia (22.2%); in MM patients 7 developed a second tumor (14.2%). Between GD1 patients one developed a MM and two a solid tumor (7.9%). Concerning the cytokine analysis, a significant difference (p<0.05) was observed in IL4; MIP-1α; MIP-1β and TNFα values between controls; MGUS; MM and GD1 patients; and also IL13 in MM and GD1. MM and GD1 not showed differences in the median values of IL4 and IL13. These groups showed significant differences in MIP-1α, MIP-1β and TNFα values. In MM there are significant differences in IL4 (p=0.012) and MIP-1α (p=0.022) between ISS 1 and ISS 3. In addition there are significant differences in MIP-1α between IgGk vs IgAL and MGUS patients that will be transformed to MM (p=0.018).(See table 1)There are not significant differences in cytokines profile between patients who developed a second neoplasia.Conclusions: These results support that GD1 and MM patients share similar proinflammatory profiles. The chronic cytokines increase in GD patients would contribute to the development of malignancies in these patients.GD1 and MM share skeletal complications, MIP-1α as osteoclast-activating factor could be a good biomarker during follow-up of GD1 or MGUS to detect patients in risk to develop bone complications. MIP-1α is described as significantly elevated in osteopenic MGUS patients(1). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association of residual plasma viremia and intima-media thickness in antiretroviral-treated patients with controlled human immunodeficiency virus infection.

BackgroundWhile residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences.MethodsThis cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL <20 copies/mL for ≥1 year). Residual HIV-VL was measured using an ultrasensitive assay (quantification limit: 1 copy/ml). Patients were categorized as having detectable (D; 1-20 copies/mL, n = 14) or undetectable (UD; <1 copies/mL, n = 33) HIV-VL. Linear regression was used to model the difference in total carotid intima-media thickness [c-IMT, measures averaged across common carotid artery (cca), bifurcation, and internal carotid artery] and cca-IMT alone across detection groups. Multivariable models were constructed for each endpoint in a forward-stepwise approach.ResultsNo significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQR = 6.8–10.9), nadir CD4+T-cell (208/mm3, IQR = 143–378), and CD4+T-cell count (555/mm3, IQR = 458–707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (p = 0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, p = 0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (p = 0.2), however there was large variability in bifurcation c-IMT measurements.ConclusionsHigher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis.

PO-1015 Impact Of Glucocorticoid Therapy In Patients With Moderate Or Severe Bronchiolitis. Preliminary Results

Objective To determine if 7 day course of systemic glucocorticoids decreases the inflammatory activity in infants with severe bronchiolitis, compared with placebo. Method and settings Prospective, randomised, double blind and placebo controlled study. Experimental group (1): iv methylprednisolone 2 mg/kg/day and/or oral prednisolone 2,5 mg/kg/day, during 7 days. Control group (2): iv/oral glucose 5% solution as placebo. Statistical valuation needed 39 patients per group. Inclusion: patients with moderate-severe bronchiolitis, under 1 year, who require hospitalisation. Recorded variables: epidemiological and clinical data; PRISM-III punctuation and HSJD bronchiolitis severity score punctuation. Laboratory data: inflammatory (IL-12, IL-2) and anti-inflammatory Interleukins (IL-4, IL-10) and Gamma-IF; at admission and 5 days. Spss19.0 ® programe was used: data was expressed as median and interquartil range (p 25–75 ). U de Mann-Whitney was indicated to quantitative data and c2 to qualitative one. Results There were randomised 100 patients (2011–2012), 94 analysed (48 group 1, 46 group2). There were 50 males (53.2%) with a median age of 37 days (p 25–75 22–57). Median PRISM was 3 points (p25–75 0–4) and median HSJD severity score 9 (p25–75 9–16). There weren’t significant differences between groups regarding sex, age, weight, or severity scores. IL response: there weren’t statistical significant differences in the IL levels at admission moment. There weren’t diferencies in gamma-IF levels between groups. There were only statistical significant differences in IL4 and IL10 at 5 days, with higher values in group 2. Conclusion Glucocorticoid therapy in patients with moderate or severe bronchiolitis probably conduces to an early stop in the anti inflammatory response.

Effects of Exosomes (EXOs) Derived by Renal Pluripotent Stem Cells (rPSCs) on the Cisplatin (Cis) Nephrotoxicity in Mice

The acute kidney injury (AKI) is characterized by Cis that induces hypoxia and generates free radicals, inflammation and apoptosis of renal tubules [1]. For these reasons it becomes essential to use strategies to prevent this acute damage. Therefore EXOs are potential tools [2]. In this study, we evaluated the EXOs derived by rPSCs on the nephrotoxicity induced by Cis. For in vitro methods, rPSCs mice (C57BL6-J) were used to obtain cultured using standard techniques following glomerular isolation by differential sieving and rPSCs. The rPSCs were characterized by immunofluorescence and FACS utilizing positive antibodies (Wnt1, CD24, PAX2 and ZO1) and negative antibodies (CD45, Thy-1 and pan cytokeratin). MSCs Mice (C57BL6-J) were used to obtained cultured using standard techniques following bone marrow isolation by differential sieving and MSCs. EXOs: rPSCs were incubed for 24 hours. Then, the EXOs were obtained by ultracentrifugation technique and characterized by Western blot utilizing CD9 and CD63. For in vivo methods, mice were treated with Cis (10mg/BW) or PBS (vehicle CTL group) during 5 days. At the 3th day of this treatment, animals were treated with EXOs (35μg/ml) derived from rPSCs in only one injection. At the end of these treatment, urine 24 hours and blood were collected by biochemical and cytokines (IL2, IL6 and IL10) analysis and kidney to evaluated for HE, caspase 3 and KI67. Results: It was observed that the rPSCs positive for the markers scored (Wnt1, CD24, PAX2 and ZO1); EXOs marked to CD9 and 63. The creatinine, urea, IL2 and IL6 increased in Cis group when compared to CTL; Cr:(2.5±0.9 vs. 1.4±0.4 mg/dl; p<0.05); U: (300±20.6 vs. 100±22.8 mg/dl; p<0.05); IL2: (1.2±0.3 vs. 0.2±0.02 pg/ml; p<0.05); IL6: (1.8±0.4 vs. 1.1±0.07pg/ml; p<0.05); Therefore, t`s not observed difference in IL10 (0.2±0.01 vs. 0.2±0.03pg/ml; p<0.05). When these animals received EXOs it was observed a decrease in Cr, U, IL2, IL6 and a significant increase of anti-inflammatory cytokines IL10 when compared to Cis group; Cr:(1.4±0.7 vs. 1.4±0.4 mg/dl; p<0.05); U: (208±32.7 vs. 100±22.8 mg/dl; p<0.05); IL2: (0.4±0.01 vs. 0.2±0.02 pg/ml; p<0.05); IL6: (0.7±0.5 vs. 1.1±0.07pg/ml; p<0.05); Therefore, ť s not observed difference in IL10 (1.1±0.02 vs. 0.2±0.03pg/ml; p<0.05). In Cis-group, the kidneys showed a small marked KI67 and intensive caspase 3 and acute tubular necrosis (ATN) expression but differently, it was highly marked for KI67 and lower expression for caspase 3 in Cis+EXOs groups and no histological ATN lesions were observed. These results strongly suggest that EXOs derived from rPSCs can minimize AKI induced by Cis. These therapeutics EXOs effects have a significant impact on renal function and holds substantial potential use especially by avoiding transplanting cells with potential adverse effects, in this experimental model.

Differences in macrophage polarization in allergic inflammation (HYP6P.271)

Abstract Lung macrophages (alternatively activated or “M2” macrophages) are critical modulators of the severity of pulmonary inflammation. M2 macrophages differentiate from mature macrophages upon exposure to Th2 cytokines, IL-4 and IL-13, abundant during allergic lung inflammation. Greater numbers of M2 macrophages were found in the lungs of female mice than male mice and in patients with asthma compared to healthy controls. SOCS1 and SOCS3 are negative regulators that control M1/M2 polarization of macrophages and they may be regulated by estrogen. We hypothesize that monocytes from asthmatic females are more responsive to IL-4/IL-13 than those from asthmatic men and that estrogen increases and androgen diminishes monocyte responses to IL-4 and IL-13. To compare sex differences in IL-4/IL-13 responses in monocytes, we purified and stimulated monocytes from male and female allergic and healthy donors with IL-4 and IL-13. We found high levels of SOCS3 in monocytes from allergic donors compared to healthy controls after IL-4 stimulation. Interestingly, expression of ERα mRNA was higher in allergic compared to healthy human macrophages, whereas ERβ and AR expression was lower. Differences in SOCS induction will provide clues to understanding sensitivity of monocyte-macrophages from allergic individuals to IL-4 and IL-13. The role of ERα, β and AR to IL-4-induced M2 macrophage polarization will help us understand why the prevalence of asthma in adult women is higher than in men.

P2.181 IL-4, IL-10 and TNF-A Profile in North-Eastern Ukrainian HIV-1 Infected Individuals with Different Level of Immunodeficiency

BackgroundAim of the study was to determine the IL-4, IL-10 and TNF-α profiles in plasma of north-eastern Ukrainian HIV-1 infected individuals with different CD4 T-cell levels.MethodsWe used a immunoassay method...

IL-10 Reduces Levels of Apoptosis in Toxoplasma gondii-Infected Trophoblasts

BackgroundTo analyze the effects of IL-10 on the HLA-G expression and the apoptosis of trophoblasts infected with Toxoplasma gondii.Methods T. gondii-infected or uninfected human trophoblasts and immortalized human placental BeWo cells were cultured with or without human IL-10. Uninfected and infected cells without IL-10 cells served as controls. HLA-G expression was measured by real-time PCR and flow cytometry, respectively. Cells apoptosis were analyzed by flow cytometry. Apoptosis associated moleculars were measured by real-time PCR and Western bolt.ResultsHLA-G expression was increased in the infected trophoblasts and BeWo cells compared to uninfected cells. Treatment of infected cells with IL-10 decreased HLA-G expression compared to infected cells while no change in treatment of uninfected cells compared with uninfected cells. Levels of apoptosis and apoptosis associated caspase-3 and caspase-8 decreased and c-FLIP levels increased in treated infected cells with IL-10 compared to infected cells and no difference in IL-10 treated uninfected cells compared to uninfected cells.ConclusionsIL-10 regulates HLA-G expression in T. gondii-infected trophoblasts. IL-10 treatment of infected trophoblasts reduced levels of apoptosis. This may contribute to the improvement in pregnancy outcomes when women infected with T. gondii treated with IL-10.

IL-4, IL-10, TNF-α profile and immunological changes in North-Eastern Ukrainian HIV-infected individuals

BackgroundCytokines play an important role in controlling the homeostasis of the immune system in HIV infection. The measurement cytokines in patients with HIV may provide additional information to complement prognostic markers and understand disease procession. Aim of the study was to determine IL-4, IL-10 and TNF-α profiles in plasma of HIV-infected individuals with different CD4 T-cell levels. MethodsQuantitative level detection of IL-4, IL-10, TNF-α was carried out by ELISA (test systems “Vektor-Best”, RF) in 78 HIV-infected people (group I: 35 persons with level of T-helpers ≥350cells/μL; group II: 43 persons with level of T-helpers ≤200cells/μL). ResultsHIV-infection was associated with an increase in plasma levels of TNF-α and IL-10. Immune imbalance due to changes in concentrations of cytokines is more pronounced in HIV-infected individuals with severe immunosuppression with CD4T lymphocyte counts ≤200cells/μL. No significant difference in IL-4 between surveyed troops and comparison group was found. ConclusionImmunological status of the patients with HIV is characterized by inefficiency of cellular compartment with imbalance of relation of immunocompetent cells and increased production of proinflammatory TNF-α and anti-inflammatory IL-10.

Regulatory T‐lymphocytes mediate amyotrophic lateral sclerosis progression and survival

In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression. To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T-lymphocytes from patients were assessed by flow cytometry. Both numbers of Tregs and their FoxP3 protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, TGF-β, IL4 and Gata3, a Th2 transcription factor, were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were accurate indicators of progression rates. No differences in IL10, Tbx21, a Th1 transcription factor or IFN-γ expression were found between slow and rapidly progressing patients. A 3.5-year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at collection and predictive of future rapid progression and attenuated survival. Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels could be used to identify rapidly progressing patients.

Tomato juice consumption reduces systemic inflammation in overweight and obese females

Tomatoes are the richest source of lycopene, a potent antioxidant. Tomato products improve antioxidant defences and reduce the risk of inflammatory diseases, at least partly, due to the presence of lycopene. Lycopene, as an anti-inflammatory agent, prevents the production of inflammatory cytokines. Obesity is a chronic inflammatory condition in which the increased level of body fat leads to an increase in circulating inflammatory mediators. We hypothesised that the consumption of a lycopene-rich food would reduce inflammation in people who are overweight or obese. A total of 106 overweight or obese female students of the Tehran University of Medical Sciences were enrolled and randomly allocated to an intervention group (n 53) or a control group (n 53) consuming 330 ml/d of tomato juice or water, respectively, for 20 d. At baseline and day 20, serum concentrations of IL-6, IL-8, high-sensitivity C-reactive protein and TNF-α were analysed by ELISA and compared between the groups. Serum concentrations of IL-8 and TNF-α decreased significantly in the intervention group compared with the control group and with baseline. Subgroup analysis indicated that this effect was confined to subjects who were overweight. Among obese subjects, serum IL-6 concentration was decreased in the intervention group compared with the control group, with no differences in IL-8 and TNF-α observed. Tomato juice reduces inflammation in overweight and obese females. Thus, increasing tomato intake may provide a useful approach for reducing the risk of inflammatory diseases such as CVD and diabetes, which are associated with obesity.

Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

BackgroundAs Chronic Fatigue Syndrome (CFS) has been known to follow Epstein-Bar virus (EBV) and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS) patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM). We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively.MethodsUsing chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection.ResultsStandard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls.ConclusionThese results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

Histone deacetylases inhibitor Trichostatin A ameliorates DNFB-induced allergic contact dermatitis and reduces epidermal Langerhans cells in mice

Histone deacetylases (HDACs) influence chromatin organization, representing a key epigenetic regulatory mechanism in cells. Trichostatin A (TSA), a potent HDAC inhibitor, has anti-tumor and anti-inflammatory effects. Allergic contact dermatitis (ACD) is a T-cell-mediated inflammatory reaction in skin and is regulated by epidermal Langerhans cells (LCs). The aim of this study was to investigate if TSA treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced ACD in mice and regulates epidermal LCs and other immune cells during ACD development. ACD was induced by sensitizing and challenging with DNFB topically. Mice were treated intraperitoneally with TSA or vehicle DMSO as a control every other day before and during induction of ACD. The ear swelling response was measured and skin biopsies from sensitized skin areas were obtained for histology. Epidermal cells, thymus, spleen and skin draining lymph nodes were collected for immune staining. TSA treatment ameliorated skin lesion severity of DNFB-induced ACD. The percentages of epidermal LCs and splenic DCs as well as LC maturation were significantly reduced in TSA-treated mice. However, TSA treatment did not significantly affect the homeostasis of conventional CD4(+) and CD8(+) T cells, Foxp3(+)CD4(+) regulatory T cells, iNKT cells, and γδ T cells in thymus, spleen and draining lymph nodes (dLNs). Furthermore, there were no significant differences in IL-4 and IFN-γ-producing T cells and iNKT cells between TSA- and DMSO-treated mice. Our findings suggest that TSA may ameliorate ACD through the regulation of epidermal LCs and HDACs could serve as potential therapeutic targets for ACD and other LCs-related skin diseases.

Echinococcus Granulosus 14-3-3 Protein: A Potential Vaccine Candidate Against Challenge with Echinococcus Granulosus in Mice

ObjectiveTo investigate the protective immunity against Echinococcus granulosus in mice immunized with rEg14-3-3. MethodsICR mice were subcutaneously immunized three times with rEg14-3-3, followed by the challenge with Echinococcus granulosus protoscoleces intraperitoneally and then sacrificed after six months of post-challenge to detect the proliferation of splenocytes by MTT assay, and to measure the secretion of IL-2, IL-4, IL-10, and IFN-γ by ELISA. The rate of reduced hydatid cyst and the levels of IgE, IgG and IgG subclasses in sera were examined. ResultsMice vaccinated with rEg14-3-3 and challenged with protoscoleces revealed significant protective immunity of 84.47%. ELISA analysis indicated that the immunized mice generated specific high levels of IgG and the prevailing isotypes of IgG were IgG1 and IgG2a. Splenocytes from mice immunized with rEg14-3-3 showed a significant proliferation response. The secretion of IFN-γ and IL-2 increased significantly in the vaccinated mice whereas there was no significant difference in IL-4 and IL-10 levels between vaccinated and control mice. ConclusionThe results indicate that the rEg14-3-3 vaccine could induce a high level of protective immunity as a promising vaccine candidate to prevent cystic echinococcosis.

Children With Islet Autoimmunity and Enterovirus Infection Demonstrate a Distinct Cytokine Profile

Cytokines are upregulated in prediabetes, but their relationship with Enterovirus (EV) infection and development of islet autoimmunity is unknown. Cytokines (n = 65) were measured using Luminex xMAP technology in a nested case-control study of 67 children with a first-degree relative with type 1 diabetes: 27 with islet autoantibodies (Ab+) and 40 age-matched persistently autoantibody negative (Ab−) control subjects. Of 74 samples, 37 (50%) were EV-PCR+ in plasma and/or stool (EV+) and the remainder were negative for EV and other viruses (EV−). Fifteen cytokines, chemokines, and growth factors were elevated (P ≤ 0.01) in Ab+ versus Ab− children (interleukin [IL]-1β, IL-5, IL-7, IL-12(p70), IL-16, IL-17, IL-20, IL-21, IL-28A, tumor necrosis factor-α, chemokine C-C motif ligand [CCL]13, CCL26, chemokine C-X-C motif ligand 5, granulocyte-macrophage colony-stimulating factor, and thrombopoietin); most have proinflammatory effects. In EV+ versus EV− children, IL-10 was higher (P = 0.005), while IL-21 was lower (P = 0.008). Cytokine levels did not differ between Ab+EV+ and Ab+EV− children. Heat maps demonstrated clustering of some proinflammatory cytokines in Ab+ children, suggesting they are coordinately regulated. In conclusion, children with islet autoimmunity demonstrate higher levels of multiple cytokines, consistent with an active inflammatory process in the prediabetic state, which is unrelated to coincident EV infection. Apart from differences in IL-10 and IL-21, EV infection was not associated with a specific cytokine profile.

Porphyromonas gingivalis infection at different gestation periods on fetus development and cytokines profile

Infective agents may affect pregnancy outcomes by deregulating homeostasis. The effects of Porphyromonas gingivalis infection before and at different gestation periods were evaluated. Wistar rats infected via subcutaneous with P. gingivalis W83, one week before mating (BM), days 1 (PR1) and 11 of gestation (PR11), and controls were evaluated, and samples were obtained at the end of gestation. P. gingivalis was detected by PCR. Cytokine was determined by ELISA. Infected rats had lower maternal gain of weight. Implantation was not observed in 2/12 BM rats. PR11 presented more fetal-placental resorptions and lower placenta/fetus weight than controls. P. gingivalis was detected in placenta and fetus. IL-6 and TNF-α levels were higher in placenta and serum of infected groups, except for TNF-α in placenta of PR1. IL-1β levels were higher in placenta of PR11, but lower in serum and placenta of PR1. There were no differences in IL-10 and PGE2 concentrations among the groups (P < 0.05). The experimental infection by P. gingivalis resulted in alterations in the gestational pattern and in fetal development. The consequences of infection at mid-gestation were more severe than at the beginning, possibly due to the induction of pro-inflammatory cytokines in the fetal compartment.

Significance of I313V mutation of NLPR3 gene in two pediatric patients

Results Both case #1 (M.T) and #2 (V.C) displayed a mild clinical phenotype (episodes of urticarial rash and arthralgia associated with elevation of acute phase reactants), compatible with FCAS and Muckle-Wells syndrome, respectively. Both patients displayed good response to NSAID and/or steroid on demand. Compared to HD controls, patients displayed enhanced and delayed IL1b secretion. This was accompanied by higher levels of lL1Ra and IL-6 without any significant differences in IL-8. Interestingly, parents carrying the mutation also displayed higher levels of secreted IL-1b compared to HD control group. Conclusion The I313V mutation is associated with a mild CAPS phenotype and with an increased IL-1b secretion.

Babassu aqueous extract (BAE) as an adjuvant for T helper (Th)1-dependent immune responses in mice of a Th2 immune response-prone strain

BackgroundThe aqueous extract of a Brazilian palm-tree fruit - the babassu - (BAE) exerts a clear immunostimulative activity in vivo. In the present work, the possibility that BAE can promote Th1 immune responses in mice of a Th2 immune response-prone strain - the BALB/c was investigated. BAE itself, and preparations consisting of Leishmania amazonensis promastigote extract (LE), adsorbed or not to Al(OH)3, and in the presence or not of BAE, were used as immunogens. LE and Al(OH)3 have been shown to preferentially elicit Th2 immune responses.ResultsThe addition of BAE to LE-containing immunogenic preparations, adsorbed or not to Al(OH)3, clearly promoted the in vitro production of interferon γ (IFN-γ), a major Th1-dependent cytokine, and not of interleukin (IL-)4 (a Th2-dependent cytokine), by LE-stimulated splenocytes of immunized BALB/c mice. It also promoted the in vivo formation of IgG2a anti-LE antibodies. However, immunization with LE by itself led to an increased production of IL-4 by LE-stimulated splenocytes, and this production, albeit not enhanced, was not reduced by the addition of BAE to the immunogen. On the other hand, the IL-4 production by LE-stimulated splenocytes was significantly lower in mice immunized with a preparation containing Al(OH)3-adsorbed LE and BAE than in mice immunized with the control preparation of Al(OH)3-adsorbed LE without BAE. Moreover, an increased production of IFN-γ, and not of IL-4, was observed in the culture supernatants of splenocytes, from BAE-immunized mice, which were in vitro stimulated with BAE or which received no specific in vitro stimulus. No differences in IL-10 (an immunoregulatory cytokine) levels in the supernatants of splenocytes from mice that were injected with BAE, in relation to splenocytes from control mice, were observed. The spontaneous ex vivo production of NO by splenocytes of mice that had been injected with BAE was significantly higher than the production of NO by splenocytes of control mice.ConclusionsBased on the results described above, BAE, or biologically active molecules purified from it, should be further investigated as a possible adjuvant, in association or not with aluminium compounds, for the preferential induction of Th1-dependent immune responses against different antigens in distinct murine strains and animal species.

Antioxidant and anticytokine effects of bovine colostrum in intestinal ischemia/reperfusion injured rat model

The objective of this study was to examine antioxidant and anticytokine effects of bovine colostrum (BC) in an intestinal ischemia/reperfusion injured rat model. Forty Sprague-Dawley rats were induced intestinal ischemia/reperfusion injury. After reperfusion the rats were given BC, 0.9% saline or low fat milk (LFM) orally. The antioxidative activities using superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT), and malondialdehyde (MDA) were analyzed in this study. Serum cytokine levels [tumor necrosis factor (TNF)-α, interlukin (IL)-1β, IL-6, and IL-10] were also checked. SOD (1.53±0.23 U/mg of protein), GSH-PX (7.62±0.66 U/mg of protein), and CAT (42.16±3.16 U/mg of protein) activities increased and MDA level (0.58±0.05 mmol/mg of protein) decreased significantly in rats fed BC compared to rats fed saline or LFM (p<0.05). TNF-α (7.63±1.31 pg/mL), IL-1β (49.43±4.43 pg/mL), and IL-6 (62.85±7.60 pg/mL) in rats fed BC were significantly lower than saline or LFM (p<0.005), whereas there was no significant difference in IL-10 (220.3±22.06 pg/mL) between experimental groups. In conclusion, BC may have both antioxidative and anticytokine effects in an intestinal ischemia/reperfusion rat model.

Expression of IL-4/IL-13 receptors in differentiating human airway epithelial cells

IL-4 and IL-13 elicit several important responses in airway epithelium including chemokine secretion and mucous secretion that may contribute to airway inflammation, cell migration, and differentiation. These cytokines have overlapping but not identical effector profiles likely due to shared subunits in their receptor complexes. These receptors are variably described in epithelial cells, and the relative expression, localization, and function of these receptors in differentiated and repairing epithelial cells are not clear. We examined IL-4/IL-13 receptor expression and localization in primary airway epithelial cells collected from normal human lungs and grown under conditions yielding both undifferentiated and differentiated cells inclusive of basal, goblet, and ciliated cell phenotypes. Gene expression of the IL-4Rα, IL-2Rγc, IL-13Rα1, and IL-13Rα2 receptor subunits increased with differentiation, but different patterns of localization and protein abundance were seen for each subunit based on both differentiation and the cell subtypes present. Increased expression of receptor subunits observed in more differentiated cells was associated with more substantial functional responses to IL-4 stimulation including increased eotaxin-3 expression and accelerated migration after injury. We demonstrate substantial differences in IL-4/IL-13 receptor subunit expression and responsiveness to IL-4 based on the extent of airway epithelial cell differentiation and suggest that these differences may have functional consequences in airway inflammation.

Increases in airway eosinophilia and a th1 cytokine during the chronic asymptomatic phase of asthma

Studies using allergen challenge models have suggested Th2 cytokines promote airway inflammation in asthma. We assessed mediators of airway inflammation during the chronic asymptomatic phase of asthma. Nine non-atopic asthma (NAA) patients, 19 atopic asthma (AA) patients, 20 atopic controls (AC), and 38 normal controls (NC) underwent sputum induction while asymptomatic. Sputum total cell counts and differentials were determined; levels of cytokines IL-4, IL-5, IL-13, GM-CSF, and IFN-gamma, and chemokines eotaxin (CCL11) and RANTES (CCL5) were measured by ELISA; and levels of eosinophil-derived neurotoxin (EDN) were measured by radioimmunoassay. NAA patients showed higher % eosinophils and total eosinophils compared to AA. NAA and AA patients showed higher IFN-gamma and EDN levels compared to AC and NC, with no differences in IL-4, IL-5, or IL-13 levels among the four groups. GM-CSF levels were higher in AA patients compared to AC or NC. In NAA, AA, and AC patients, % eosinophils and EDN levels correlated positively with IFN-gamma, GM-CSF, eotaxin, and RANTES, but not with IL-5 levels. Baseline airway inflammation of intrinsic and extrinsic asthma is characterized by eosinophilic inflammation and the Th1 cytokine, IFN-gamma. GM-CSF, instead of IL-5, and chemokines may coordinate airway eosinophilia during the chronic asymptomatic phase of asthma.