Leptin deficiency enhances sensitivity to endotoxin-induced lethality

1999 ◽  
Vol 276 (1) ◽  
pp. R136-R142 ◽  
Author(s):  
Raffaella Faggioni ◽  
Giamila Fantuzzi ◽  
Cem Gabay ◽  
Arthur Moser ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Serum Levels ◽  
Interferon Γ ◽  
Serum Glucose ◽  
Serum Leptin ◽  
Inflammatory Protein ◽  
Increased Sensitivity ◽  
Necrosis Factor

Leptin is induced by lipopolysaccharide (LPS) and cytokines. We investigated the role of leptin in LPS-induced toxicity using leptin-deficient ( ob/ ob) and leptin receptor-deficient ( db/ db) mice. Sensitivity to LPS-induced mortality is significantly greater in ob/ obmice compared with their own lean littermates but not in db/ dbmice. LPS reduced serum glucose in both ob/ oband db/ dbmice but induced corticosterone only in db/ dbmice. Despite the very high basal levels of serum leptin in db/ dbmice, a twofold increase in serum leptin levels was observed after LPS in both db/ dbmice and their lean littermates. No differences were detected in LPS-induced serum levels of interleukin (IL)-1β, tumor necrosis factor, macrophage inflammatory protein-1α, and interferon-γ in ob/ obmice compared with their own littermates. In contrast, a blunted induction of IL-10 and IL-1 receptor antagonist (IL-1Ra) was observed in ob/ obmice compared with their littermates. In vitro, leptin induced IL-1Ra production and upregulated the IL-1Ra induction by LPS in macrophages. Moreover, treatment with leptin reversed the increased sensitivity to LPS-induced lethality found in ob/ obmice. These results suggest that leptin participates in the host response to inflammation by modulating the host immune and cytokine responses after LPS.

Multiple Inhibitory Cytokines Induce Deregulated Progenitor Growth and Apoptosis in Hematopoietic Cells From Fac−/− Mice

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4092-4098 ◽  
Author(s):  
Laura S. Haneline ◽  
Hal E. Broxmeyer ◽  
Scott Cooper ◽  
Giao Hangoc ◽  
Madeleine Carreau ◽  
...  
Keyword(s):  
Hematopoietic Cells ◽  
Interferon Γ ◽  
Major Mechanism ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Murine Homologue ◽  
Anemia Group ◽  
Factor Α ◽  
Necrosis Factor

Abstract We used a murine model containing a disruption of the murine homologue (Fac) of Fanconi Anemia group C (FAC) to evaluate the role of Fac in the pathogenesis of bone marrow (BM) failure. Methylcellulose cultures of BM cells fromFac−/− and Fac+/+ mice were established to examine the growth of multipotent and lineage-restricted progenitors containing inhibitory cytokines, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1α (MIP-1α). Clonogenic growth of Fac−/− progenitors was reduced by 50% at 50- to 100-fold lower concentrations of all inhibitory cytokines evaluated. We hypothesized that the aberrant responsiveness to inhibitory cytokines in clonogenic cells may be a result of deregulated apoptosis. To test this hypothesis, we performed the TUNEL assay on purified populations of primary BM cells enriched for hematopoietic progenitors or differentiated myeloid cells. After stimulation with TNF-α, accentuated apoptosis was observed in both populations of Fac−/− cells. In addition, deregulated apoptosis was also noted in the most immature phenotypic population of hematopoietic cells after stimulation with MIP-1α.Together these data suggest a role of Fac in affecting the signaling of multiple cytokine pathways and support cytokine-mediated apoptosis as a major mechanism responsible for BM failure observed in FA patients.

scholarly journals Comprehensive analysis of inflammatory markers in chronic thromboembolic pulmonary hypertension patients

2014 ◽  
Vol 44 (4) ◽  
pp. 951-962 ◽  
Author(s):  
Diana Zabini ◽  
Akos Heinemann ◽  
Vasile Foris ◽  
Chandran Nagaraj ◽  
Patrick Nierlich ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Serum Levels ◽  
Interferon Γ ◽  
Walking Distance ◽  
Healthy Controls ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Protein ◽  
Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with chronic inflammation but the pathological mechanisms are largely unknown. Our study aimed to simultaneously profile a broad range of cytokines in the supernatant of pulmonary endarterectomy (PEA) surgical material, as well as prospectively in patients with CTEPH to investigate whether circulating cytokines are associated with haemodynamic and physical characteristics of CTEPH patients.Herein, we show that PEA specimens revealed a significant upregulation of interleukin (IL)-6, monocyte chemoattractant protein-1, interferon-γ-induced protein-10 (IP)-10, macrophage inflammatory protein (MIP)1α and RANTES compared to lung tissue from healthy controls.In prospectively collected serum, levels of IL-6, IL-8, IP-10, monokine induced by interferon-γ (MIG) and MIP1α were significantly elevated in CTEPH patients compared to age- and sex-matched healthy controls. In serum of idiopathic pulmonary arterial hypertension (IPAH) patients, only IP-10 and MIG were significantly increased. In CTEPH but not in IPAH, IP-10 was negatively correlated with cardiac index, 6-min walking distance and carbon monoxide diffusion capacity. In vitro, IP-10 significantly increased migration of freshly isolated adventitial fibroblasts.Our study is the first to show that IP-10 secretion is associated with poor pulmonary haemodynamics and physical capacity in CTEPH and might be involved in the pathological mechanism of PEA tissue formation.

Role of tumor necrosis factor-α, interferon-γ and Fas-ligand on in vitro nitric oxide activity in the corpus luteum

Cytokine ◽  
2013 ◽  
Vol 64 (1) ◽  
pp. 18-21 ◽  
Author(s):  
A.M. Galvão ◽  
Anna Z. Szóstek ◽  
Dariusz J. Skarzynski ◽  
Graça M. Ferreira-Dias
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Fas Ligand ◽  
Interferon Γ ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis

2022 ◽  
Vol 12 ◽  
Author(s):  
Yoshimasa Imoto ◽  
Shigeharu Ueki ◽  
Yukinori Kato ◽  
Kanako Yoshida ◽  
Taiyo Morikawa ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Elevated Serum ◽  
Serum Levels ◽  
Histological Evaluation ◽  
Dependent Manner ◽  
Epithelial Surface ◽  
Serum Leptin

Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated.Objective: To determine whether the serum levels of leptin are altered in patients with ECRS.Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient’s serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression.Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p < 0.0001 vs. ECRS; p < 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p < 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p < 0.01) and the number of eosinophils in NPs (r = 0.5109, p < 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p < 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p < 0.05).Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.

scholarly journals SAT0296 SERUM LEPTIN LEVELS IN SYSTEMIC SCLEROSIS PATIENTS WITH ELECTROCARDIOGRAPHIC ABNORMALITIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1093.1-1093
Author(s):  
G. Pellegrino ◽  
K. Stefanantoni ◽  
F. Facioni ◽  
C. Angelelli ◽  
A. Gigante ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Chronic Diseases ◽  
Cardiac Fibrosis ◽  
Serum Levels ◽  
High Serum ◽  
Control Group ◽  
Pathologic Finding ◽  
Serum Leptin ◽  
Ecg Abnormalities

Background:Electrocardiographic (ECG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) cases and they are associated with other systemic manifestations as well as with a worse prognosis. There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic and therapeutic approaches to patients with ECG abnormalities, due to their actual low sensitivity and specificity. Adipokines are circulating proteins that appear dysregulated in SSc and leptin in particular is synthesized in response to inflammatory conditions and seems to play a proinflammatory and pro-fibrotic action in SSc. Interesting, many studies in the last years have underlined its role in the cardiac remodeling mechanisms and in the development of cardiac fibrosis in other chronic diseases.Objectives:Aim of our study is to evaluate the role of leptin in the development of cardiac rhythm disorders (CRD) during SSc. Furthermore, by the analysis of the clinical and demographical parameters of our SSc patients, we tried to define other possible features associated with increased serum leptin concentration.Methods:We included eighty-five SSc patients, fulfilling the 2013 ACR/EULAR classification criteria, attending the Regional Rare Disease Center of Policlinico Umberto I of Rome. Fifty presented significant CRD at non-invasive diagnostic techniques (12 Lead ECG, 24-hour Holter ECG). Demographic, clinical, conventional cardiovascular risk factors were examined; instrumental and laboratory assessments were obtained, together with ECG recordings. Thirty-five SSc patients without pathologic finding at ECG traces, matched for demographic and clinical features, were recruited as the control group. In all cases, after obtaining written informed consent, blood samples were taken to measure serum levels of leptin using an ELISA assay (Life Technologies-Italia).Results:The fifty SSc patients with CRD (mean age 51±15 years; F:M 41:9) had pulmonary fibrosis (PF) in 32 cases (64%) and a BMI >25Kg/m2in 22 (44%) while in the control group of thirty-five SSc patients (mean age 49±16 years; F:M 33:2) PF was found in 15 (43%) and a BMI >25Kg/m2in 9 (35%); We detected significantly higher median values of serum leptin in SSc patients with CRD compared to the control group (12027 pg/ml IQR 12314 versus 6392 pg/ml IQR 7103;p 0,0009). Additionally, SSc patients with a BMI> 25 kg/m2(31 cases) as well as those with PF (47 cases) showed a significantly higher median serum leptin levels compared to those with BMI <25 kg/m2(13161 pg/ml IQR 13610 versus 8187 pg/ml IQR 8255;p 0,0008) and those without PF (11740 pg/ml IQR 11940 versus 7616 pg/ml IQR 7855;p 0,0079).Conclusion:To our knowledge this is the first report on high serum levels of leptin in SSc patients with CRD that also confirms its increase in those cases with a BMI >25 kg/m2and with PF, according to scientific literature data. The role of leptin in the pathogenesis of SSc remains unclear although it is already known its involvement in the development of cardiac fibrosis during other chronic diseases. On the basis of these results we speculate on leptin involvement in the pathogenesis of CRD during SSc, although further studies are needed with larger cohort of patients.References:[1]Vacca A et al. Rheumatology, 2014[2]Tyndall AJ et al. Ann Rheum Dis, 2010[3]Muresan L et al. Iran J Pub Health, 2017[4]Sanna T et al. Indian Pacing Electrophysiol J, 2009[5]Riccieri V et al. Clin Exp Rheumatol, 2011[6]Żółkiewicz J et al. Arch Dermatol Res, 2019[7]Huby AC et al. Circulation, 2015[8]Shulze PC et al. Clin Chim Acta, 2005[9]Van de Hoogen F et al. Arthritis Rheum, 2013[10]Gui X et al. Biochem Biophys Res Commun, 2018Disclosure of Interests:Greta Pellegrino: None declared, Katia Stefanantoni Consultant of: ItalfarmacoBoehringer Ingelheim, Fausta Facioni: None declared, Carlotta Angelelli: None declared, Antonietta Gigante: None declared, Roberto Badagliacca: None declared, Carmine Dario Vizza: None declared, Sergio Morelli: None declared, Edoardo Rosato: None declared, Valeria Riccieri: None declared

scholarly journals Triglyceride-rich lipoproteins prevent septic death in rats.

1995 ◽  
Vol 182 (1) ◽  
pp. 267-272 ◽  
Author(s):  
T E Read ◽  
C Grunfeld ◽  
Z L Kumwenda ◽  
M C Calhoun ◽  
J P Kane ◽  
...  
Keyword(s):  
Lipid Emulsion ◽  
Tumor Necrosis ◽  
Lethal Dose ◽  
Cecal Ligation ◽  
Serum Levels ◽  
Cecal Ligation And Puncture ◽  
Gram Negative ◽  
Necrosis Factor ◽  
Serum Tumor Necrosis

Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P &lt; or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P &lt; or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P &lt; or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P &lt; or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P &lt; or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis.

Tumor necrosis factor α and interferon γ genes polymorphisms and serum levels in pancreatic adenocarcinoma

Neoplasma ◽  
2009 ◽  
Vol 56 (1) ◽  
pp. 56-62 ◽  
Author(s):  
R. Talar-Wojnarowska ◽  
A. Gasiorowska ◽  
B. Smolarz ◽  
H. Romanowicz-Makowska ◽  
A. Kulig ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Pancreatic Adenocarcinoma ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Serum Levels ◽  
Interferon Γ ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Role of Regulatory B Cells in the Progression of Cervical Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zhifang Chen ◽  
Yuejie Zhu ◽  
Rong Du ◽  
Nannan Pang ◽  
Fengbo Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Intraepithelial Neoplasia ◽  
Serum Levels ◽  
Hpv Infection ◽  
Control Group ◽  
Cell Percentage

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.

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