Interactions of tumor necrosis factor and granulocytes with pulmonary vascular resistance

1991 ◽  
Vol 71 (6) ◽  
pp. 2338-2345 ◽  
Author(s):  
I. Mayers ◽  
D. Johnson ◽  
T. Hurst ◽  
T. To
Keyword(s):  
Tumor Necrosis Factor ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Whole Blood ◽  
Tumor Necrosis ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Tnf Alpha ◽  
Group 2 ◽  
Necrosis Factor ◽  
Group 1

We studied the effects of endotoxin and tumor necrosis factor (TNF-alpha) on hypoxic pulmonary vasoconstriction (HPV) in 12 isolated perfused canine lung lobes. Group 1 lobes were perfused with whole blood, and group 2 lobes were perfused with granulocyte-depleted blood. All lobes were sequentially ventilated with control (35% O2) and hypoxic (3% O2) gas mixtures before and after receiving TNF-alpha. After TNF-alpha, group 2 lost HPV but group 1 retained HPV. After TNF-alpha, total pulmonary vascular resistance decreased in group 2 from 0.085 +/- 0.013 to 0.049 +/- 0.016 cmH2O.ml-1.min (P less than 0.05). We conclude that TNF-alpha acts as a pulmonary vascular vasodilator. In lobes perfused with whole blood, HPV is paradoxically preserved. We speculate that in the presence of cells rich in TNF-alpha receptors, i.e., granulocytes, the circulating levels of TNF-alpha are depressed and full expression of its vascular effects is blunted.

scholarly journals Plasma soluble tumor necrosis factor-alpha receptors circulate in proportion to leptin levels during the menstrual cycle in lean but not in obese women

2000 ◽  
pp. 235-241 ◽  
Author(s):  
JM Fernandez-Real ◽  
C Gutierrez ◽  
J Vendrell ◽  
R Casamitjana ◽  
W Ricart
Keyword(s):  
Menstrual Cycle ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Follicular Phase ◽  
Tnf Alpha ◽  
Obese Women ◽  
Necrosis Factor Alpha ◽  
Group 2 ◽  
Necrosis Factor ◽  
Group 1

OBJECTIVE: In recent studies serum leptin levels were significantly higher in the luteal phase than in the follicular phase, but the mechanism of changing leptin levels are unknown. Several research lines indicate a potential role for tumor necrosis factor (TNF-alpha) in ovulation and reproductive events. As TNF-alpha appears to regulate leptin secretion, we speculated that TNF-alpha might be involved in leptin variations during the menstrual cycle. DESIGN AND METHODS: Nine healthy never obese and ten overweight normally cycling women were studied. TNF-alpha action - through the plasma levels of the soluble fraction of the tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) - and leptin concentrations were measured in the follicular (F), peri-ovulatory (PO) and luteal phases (L) of their menstrual cycles. RESULTS: Circulating leptin levels were significantly associated with the stage of the menstrual cycle (P<0.001), being higher in PO and L phases. However, only three of ten overweight subjects vs eight of nine lean women (Chi square P=0.014 after Fisher's exact test) showed significantly higher leptin levels in the PO and L than in the F phase (95% confidence interval (95% CI) of the differences, 3.7 to 10.2 ng/ml, paired t-test P=0.001). In these women (group 1), the changes in leptin levels parallelled the variations observed in plasma sTNFR1 (2.50+/-0.1 vs 2.11+/-0.05 ng/ml, P<0.0001, 95% CI, 0.21 to 0.56) and sTNFR2 levels (5.19+/-0.28 vs 4.55+/-0.25 ng/ml, P<0.0001, 95% CI, 0. 47 to 0.81). In the remaining women (group 2), leptin (95% CI, -1 to 9.2 ng/ml, P=not significant (NS)), sTNFR1 (95% CI, -0.3 to 0.14 ng/ml, P=NS) and sTNFR2 levels (95% CI, -0.95 to 0.39 ng/ml, P=NS) were essentially unaltered throughout the menstrual cycle. Group 2 women were similar in age (36.1+/-2.9 vs 37.3+/-1.4 years) and significantly overweight (body mass index 31+/-2.9 vs 23.9+/-1. 2 kg/m(2)) compared with group 1 women. A negative correlation was observed between leptin levels in the follicular phase and the change in plasma leptin from F to L phase in all subjects (r=-0.67, P=0.002). CONCLUSIONS: Circulating leptin and sTNFRs levels change significantly during the menstrual cycle of most lean women. In contrast, the levels of these molecules remain essentially unaltered during the F, PO and L phases in the majority of overweight women. Obesity might be associated not only with blunted diurnal excursions and dampened pulsatility, but also with blunted excursions during the menstrual cycle.

Therapeutic hypercapnia prevents bleomycin-induced pulmonary hypertension in neonatal rats by limiting macrophage-derived tumor necrosis factor-α

2012 ◽  
Vol 303 (1) ◽  
pp. L75-L87 ◽  
Author(s):  
A. Charlotte P. Sewing ◽  
Crystal Kantores ◽  
Julijana Ivanovska ◽  
Alvin H. Lee ◽  
Azhar Masood ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Right Ventricular ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Tumor Necrosis ◽  
Neonatal Rat ◽  
Tnf Α ◽  
Necrosis Factor

Bleomycin-induced lung injury is characterized in the neonatal rat by inflammation, arrested lung growth, and pulmonary hypertension (PHT), as observed in human infants with severe bronchopulmonary dysplasia. Inhalation of CO2 (therapeutic hypercapnia) has been described to limit cytokine production and to have anti-inflammatory effects on the injured lung; we therefore hypothesized that therapeutic hypercapnia would prevent bleomycin-induced lung injury. Spontaneously breathing rat pups were treated with bleomycin (1 mg/kg/d ip) or saline vehicle from postnatal days 1–14 while being continuously exposed to 5% CO2 (PaCO2 elevated by 15–20 mmHg), 7% CO2 (PaCO2 elevated by 35 mmHg), or normocapnia. Bleomycin-treated animals exposed to 7%, but not 5%, CO2, had significantly attenuated lung tissue macrophage influx and PHT, as evidenced by normalized pulmonary vascular resistance and right ventricular systolic function, decreased right ventricular hypertrophy, and attenuated remodeling of pulmonary resistance arteries. The level of CO2 neither prevented increased tissue neutrophil influx nor led to improvements in decreased lung weight, septal thinning, impaired alveolarization, or decreased numbers of peripheral arteries. Bleomycin led to increased expression and content of lung tumor necrosis factor (TNF)-α, which was found to colocalize with tissue macrophages and to be attenuated by exposure to 7% CO2. Inhibition of TNF-α signaling with the soluble TNF-2 receptor etanercept (0.4 mg/kg ip from days 1–14 on alternate days) prevented bleomycin-induced PHT without decreasing tissue macrophages and, similar to CO2, had no effect on arrested alveolar development. Our findings are consistent with a preventive effect of therapeutic hypercapnia with 7% CO2 on bleomycin-induced PHT via attenuation of macrophage-derived TNF-α. Neither tissue macrophages nor TNF-α appeared to contribute to arrested lung development induced by bleomycin. That 7% CO2 normalized pulmonary vascular resistance and right ventricular function without improving inhibited airway and vascular development suggests that vascular hypoplasia does not contribute significantly to functional changes of PHT in this model.

scholarly journals Tumor necrosis factor (TNF)-induced protein phosphorylation in a human rhabdomyosarcoma cell line is mediated by 60-kD TNF receptors (TR60)

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2211-2220 ◽  
Author(s):  
A Mire-Sluis ◽  
A Meager
Keyword(s):  
Tumor Necrosis Factor ◽  
Protein Phosphorylation ◽  
Cell Line ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Tnf Receptors ◽  
Protein Kinase C Inhibitors ◽  
Rhabdomyosarcoma Cell Line ◽  
Rhabdomyosarcoma Cell ◽  
Necrosis Factor

Abstract In the present study, we used a cloned derivative, KYM-1D4, of the human rhabdomyosarcoma cell line, KYM-1, known to express high numbers of the two tumor necrosis factor (TNF) receptors, TR60 and TR80, and to be highly sensitive to TNF alpha-mediated cytotoxicity/antiproliferation, to investigate the role of TR60 and TR80 in protein phosphorylation. Using permeabilized KYM-1D4 cells, it was found that TNF alpha strongly induced phosphorylation of proteins of molecular weight 80, 65, 58, 42, and 30 kD. Addition of a monoclonal antibody (MoAb) against TR60 was shown to induce cytotoxicity/antiproliferation in KYM-1D4 cells and the same pattern of protein phosphorylation as TNF alpha, whereas addition of an MoAb against TR80 was both noncytotoxic and ineffective in inducing protein phosphorylation. In contrast, in a highly TNF alpha-resistant KYM-1- derived cell line, 37B8R, no protein phosphorylation was induced with either TNF alpha or the agonistic anti-TR60 MoAb. However, when 37B8R was allowed to revert to partial TNF sensitivity by culture in the absence of TNF alpha, the resultant cell line, 37B8S, was found to regain inducibility of protein phosphorylation by TNF alpha. These results indicate that expression of functional TR60 in KYM-1-related cell lines is principally involved in TNF-mediated cytotoxicity/antiproliferation and is necessary for the induction of protein phosphorylation. Nevertheless, the latter, although apparently strongly associated with cytotoxicity, was probably involved in protective mechanisms because protein kinase C inhibitors that inhibited TNF alpha and anti-TR60-induced phosphorylation increased the cytotoxic/antiproliferative response to these mediators.

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells

1995 ◽  
Vol 269 (6) ◽  
pp. G953-G960 ◽  
Author(s):  
M. Mehran ◽  
E. Seidman ◽  
R. Marchand ◽  
C. Gurbindo ◽  
E. Levy
Keyword(s):  
Lipid Metabolism ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Low Density Lipoproteins ◽  
Tnf Alpha ◽  
Low Density ◽  
Necrosis Factor Alpha ◽  
Apo B ◽  
Factor Alpha ◽  
Necrosis Factor

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

Tumor Necrosis Factor-α Hyper-Responsiveness to Endotoxin in Whole Blood Is Associated with Chronic Bronchitis in Farmers

2005 ◽  
Vol 10 (1) ◽  
pp. 39-44 ◽  
Author(s):  
G. Patrick Lambert ◽  
John R. Spurzem ◽  
Debra J. Romberger ◽  
Todd A. Wyatt ◽  
Elizabeth Lyden ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Chronic Bronchitis ◽  
Whole Blood ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

ROLE OF INTER LEUKIN 10 AND TUMOR NECROSIS FACTOR-ΑLPHA IN PANCREATITIS

2021 ◽  
pp. 14-17
Author(s):  
Mukherjee.J. R ◽  
Mukherjee. B ◽  
Roy. S ◽  
Jana. D ◽  
Bandopadhyay. S ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
General Surgery ◽  
Tumor Necrosis ◽  
Cell Injury ◽  
Gall Stone ◽  
Tnf Alpha ◽  
Tnf Α ◽  
The Mean ◽  
Necrosis Factor

Background: Pancreatic acinar cell injury triggers the synthesis and release of pro-inammatory cytokines and chemokines. The involvement of several pro-inammatory and anti-inammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-33 and tumor necrosis factor-α is involved in the pathogenesis of pancreatitis. Aim: This study aims to validate the role of activation of TNF-alpha and IL-10 as a biomaker marker in patients with Pancreatitis in Indian subcontinent.Material and methods: 50 Patients of Pancreatitis attending general surgery OPD and admitted to General Surgery department of SSKM Hospital, Kolkata, West Bengal, India were taken. Result: It was found that in alcoholic, the mean TNF - α (mean±s.d.) of the patients was 19.4027 ± 8.3275 pg/ml. In ascites, the mean TNF - α (mean±s.d.) of the patients was 19.9767 ± 2804 pg/ml. In chronic, the mean TNF - α (mean±s.d.) of the patients was 18.8533 ± 8.4674 pg/ml. In gall stone, the mean TNF - α (mean±s.d.) of the patients was 16.3421 ± 9.9499 pg/ml. In osteoarthritis, the mean TNF - α (mean±s.d.) of the patients was 12.4750 ± 8.3085 pg/ml. Distribution of mean TNF - α vs. association was not statistically signicant (p=0.7309).Conclusion: It was found that IL10 was higher in Ascites patients though it was not statistically signicant. TNF alpha was higher in Ascites patients. TNF alpha was higher in normal Pancreatitis.

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