TNF-α tolerance blocks LPS-induced hypophagia but LPS tolerance fails to prevent TNF-α-induced hypophagia

1998 ◽  
Vol 274 (3) ◽  
pp. R741-R745 ◽  
Author(s):  
M. H. Porter ◽  
M. Arnold ◽  
W. Langhans
Keyword(s):  
Food Intake ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Male Rats ◽  
Cross Tolerance ◽  
Dark Cycle ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

To investigate the role of tumor necrosis factor-α (TNF-α) in bacterial lipopolysaccharide (LPS)-induced hypophagia, we tested whether a cross tolerance between LPS and TNF-α exists with respect to their anorectic effects. Only the first of three subsequent intraperitoneal injections of LPS (100 μg/kg body wt) given every second day at dark onset (12:12-h light-dark cycle) led to a significant reduction of food intake in male rats. Likewise, intraperitoneal injections of human recombinant TNF-α (150 μg ≥ 3 × 106U/kg body wt) also resulted in tolerance to its hypophagic effect. LPS tolerance did not alter the hypophagic response to subsequently injected TNF-α ( n = 14). However, TNF-α pretreatment completely blocked the hypophagic response to LPS ( n = 14). The results demonstrate that tolerance to the hypophagic effect of exogenous TNF-α is sufficient to eliminate LPS-induced hypophagia. This is consistent with the hypothesis that endogenous TNF-α plays a major role in LPS-induced hypophagia. The ineffectiveness of LPS tolerance to attenuate TNF-α-induced hypophagia is compatible with findings demonstrating that reduced TNF-α production is an important feature of LPS tolerance.

The Role of Tumor Necrosis Factor-α (TNF-α) Polymorphisms in Gastric Cancer: a Meta-Analysis

2021 ◽  
Author(s):  
Maryam Gholamalizadeh ◽  
Samaneh Mirzaei Dahka ◽  
Hadi Sedigh Ebrahim-Saraie ◽  
Mohammad Esmail Akbari ◽  
Azam Pourtaheri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Meta Analysis ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract P317: Sex Differences in the Hemodynamic and Sympathetic Responses to Centrally Administered Tumor Necrosis Factor-α in Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Shun-Guang Wei ◽  
Yang Yu ◽  
Robert B Felder
Keyword(s):  
Heart Failure ◽  
Sex Differences ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Female Rats ◽  
Male Rats ◽  
Tnf Α ◽  
Estrogen Effect ◽  
Factor Α ◽  
Necrosis Factor

Introduction: Accumulating evidence indicates that sex differences exist in the clinical and experimental outcomes of various cardiovascular diseases. In addition to its protective effect on renin-angiotensin system activity, estrogen has an anti-inflammatory influence. The central actions of pro-inflammatory cytokines (PICs) contribute significantly to cardiovascular and autonomic dysfunction in hypertension and heart failure. In male adult rat, central administration of PICs induces substantial increases in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA), and blocking PICs reduces sympathetic excitation in experimental models of hypertension and heart failure. Whether PICs have similar central sympatho-excitatory effects in the female rat remains unknown. Hypothesis: We hypothesized that female rats may be protected from the central cardiovascular and autonomic effects of PICs. Methods: Urethane anesthetized male and female Sprague Dawley rats (10-12 weeks) underwent an intracerebrovascular (ICV) injection of the prototypical PIC tumor necrosis factor-α (TNF-α, 100 ng). BP (mmHg), HR (beats/min) and RSNA (% change) responses were continuously recorded for 4-5 hours. Results: In male rats (n=6), ICV TNF-α induced a dramatic and long-lasting increase (*p<0.001 vs. baseline) in BP (23.1 ± 2.5*), HR (82 ± 8*) and RSNA (109.5 ± 4.3 %*), that began within 20-30 mins and peaked at 90-120 mins after ICV injection. In the female rats (n=6), ICV TNF-α elicited significantly (p<0.05) smaller increases (*p<0.001 vs. baseline) in BP (14.8 ± 1.8*), HR (55 ± 6*) and RSNA (78.5 ± 6.3*), compared with the male rats. Conclusion: These data demonstrate a sex difference in the cardiovascular and sympathetic responses to centrally administered PICs. Whether the observed differences can be explained by an estrogen effect on TNF-α signaling per se or by an estrogen effect on TNF-α-induced renin-angiotensin activity remains to be determined. However, a reduced response of female rats to central inflammation may be an important contributor to sex differences in pathophysiology of hypertension and heart failure.

Association Between Tumor Necrosis Factor-α Gene Polymorphism and Sasang Constitution in Cerebral Infarction

2005 ◽  
Vol 33 (04) ◽  
pp. 547-557 ◽  
Author(s):  
Jae-Young Um ◽  
Jae-Heung Lee ◽  
Jong-Cheon Joo ◽  
Kyung-Yo Kim ◽  
Eun-Hee Lee ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cerebral Infarction ◽  
Promoter Region ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Sasang Constitution ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

During the last decade, a growing corpus of evidence has indicated an important role of cytokines in the development of brain damage following cerebral ischemia. Tumor necrosis factor-α (TNF-α), a potent immunomodulator and pro-inflammatory cytokine, has been implicated in many pathological processes. In this study, we examined whether promoter region polymorphism in the TNF-α gene at position –308 affects the odds of cerebral infarction (CI) and whether genetic risk is enhanced by Sasang constitutional classification. Two hundred and twelve CI patients and 610 healthy controls were genotyped and determined according to Sasang constitutional classification. A significant decrease was found for the TNF-α A allele in CI patients compared with controls ( p = 0.033, odds ratio, OR: 0.622). However, there was no significant association between TNF-α polymorphism and Sasang constitution in CI patients. Our finding suggests that TNF-α promoter region polymorphism is responsible for susceptibility to CI in Koreans.

scholarly journals Inhibition of Inflammation Mediated Through the Tumor Necrosis Factor α Biochemical Pathway Can Lead to Favorable Outcomes in Alzheimer Disease

2017 ◽  
Vol 9 ◽  
pp. 117957351772251 ◽  
Author(s):  
Daniah Shamim ◽  
Michael Laskowski
Keyword(s):  
Tumor Necrosis Factor ◽  
Alzheimer Disease ◽  
Immune Modulation ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Sodium Hydrosulfide ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) inhibitors have long been used as disease-modifying agents in immune disorders. Recently, research has shown a role of chronic neuroinflammation in the pathophysiology of neurodegenerative diseases such as Alzheimer disease, and interest has been generated in the use of anti-TNF agents and TNF-modulating agents for prevention and treatment. This article extensively reviewed literature on animal studies testing these agents. The results showed a role for direct and indirect TNF-α inhibition through agents such as thalidomide, 3,6-dithiothalidomide, etanercept, infliximab, exendin-4, sodium hydrosulfide, minocycline, imipramine, and atorvastatin. Studies were performed on mice, rats, and monkeys, with induction of neurodegenerative physiology either through the use of chemical agents or through the use of transgenic animals. Most of these agents showed an improvement in cognitive function as tested with the Morris water maze, and immunohistochemical and histopathological staining studies consistently showed better outcomes with these agents. Brains of treated animals showed significant reduction in pro-inflammatory TNF-α and reduced the burden of neurofibrillary tangles, amyloid precursor protein, and β-amyloid plaques. Also, recruitment of microglial cells in the central nervous system was significantly reduced through these drugs. These studies provide a clearer mechanistic understanding of the role of TNF-α modulation in Alzheimer disease. All studies in this review explored the use of these drugs as prophylactic agents to prevent Alzheimer disease through immune modulation of the TNF inflammatory pathway, and their success highlights the need for further research of these drugs as therapeutic agents.

scholarly journals Inactive Rhomboid Protein 2 Mediates Intestinal Inflammation by Releasing Tumor Necrosis Factor–α

2019 ◽  
Vol 26 (2) ◽  
pp. 242-253
Author(s):  
Jee Hyun Kim ◽  
Sung Wook Hwang ◽  
Jaemoon Koh ◽  
Jaeyoung Chun ◽  
Changhyun Lee ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Immune Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Intestinal Inflammation ◽  
Converting Enzyme ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Inactive rhomboid 2 (iRhom2) is an essential molecule required for the maturation of tumor necrosis factor–α–converting enzyme in immune cells, which regulates TNF-α release. The aim of this study was to investigate the role of iRhom2 in intestinal inflammation.

Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti–tumor necrosis factor-α antibody therapy

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 474-482 ◽  
Author(s):  
Helen A. Papadaki ◽  
Heraklis D. Kritikos ◽  
Vasilis Valatas ◽  
Dimitrios T. Boumpas ◽  
George D. Eliopoulos
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
Chronic Disease ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Anemia Of Chronic Disease ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Abstract Circumstantial evidence has implicated tumor necrosis factor α (TNF-α) in the pathogenesis of anemia of chronic disease (ACD) in rheumatoid arthritis (RA). We investigated the role of TNF-α in erythropoiesis of patients with active RA (n = 40) and the effect of anti–TNF-α antibody administration (cA2). Patients with RA had lower numbers of CD34+/CD71+ and CD36−/glycophorin A+ (glycoA+) bone marrow (BM) cells and increased proportions of apoptotic cells within the CD34+/CD71+ and CD36+/glycoA+ cell compartments, compared to healthy controls (n = 24). Erythroid burst-forming units (BFU-Es) obtained by BM mononuclear or purified CD34+ cells were significantly lower in RA patients compared to controls. These abnormalities were more pronounced among patients with ACD. Increased TNF-α levels in patient long-term BM culture supernatants inversely correlated with BFU-Es and hemoglobin levels and positively with the percentage of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells. Following cA2 therapy, a normalization was documented in the number of CD34+/CD71+ and CD36−/glycoA+ cells, the number of BFU-Es, and the proportion of apoptotic CD34+/CD71+ and CD36+/glycoA+ cells, which was associated with a significant increase in hemoglobin levels compared to baseline. Recovery from anemia was more prominent in patients with ACD. The exogenous addition of an anti–TNF-α antibody in the cultures increased BFU-E number in patients prior to cA2 treatment but not after treatment, further substantiating the inhibitory role of TNF-α on patients' erythropoiesis. We conclude that TNF-α–mediated apoptotic depletion of BM erythroid cells may account for ACD in RA and that cA2 administration may ameliorate ACD in these patients by down-regulating the apoptotic mechanisms involved in erythropoiesis.

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