Effect of heat stress on LPS-induced fever and tumor necrosis factor

1997 ◽  
Vol 273 (3) ◽  
pp. R858-R863 ◽  
Author(s):  
M. J. Kluger ◽  
K. Rudolph ◽  
D. Soszynski ◽  
C. A. Conn ◽  
L. R. Leon ◽  
...  
Keyword(s):  
Heat Stress ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Subjects ◽  
Core Body Temperature ◽  
Heat Exposure ◽  
Male Rats ◽  
Long Term Effects ◽  
Inflammatory Stimuli ◽  
Necrosis Factor

Exposure to heat stress leads to both short-term and long-term effects on morbidity. Male rats were exposed to a high ambient temperature of 40 degrees C, which resulted in biotelemetered core body temperature rising to approximately 42 degrees C. This treatment led to a marked enhancement in lipopolysaccharide (LPS)-induced fever at 24 h after exposure to heat stress. The increase in fever was accompanied by a significant suppression in the circulating concentration of tumor necrosis factor. Heat-shock protein-70 measured in liver was elevated by the heat exposure (but not further elevated by the injection of LPS). An enhanced fever to LPS and other inflammatory stimuli found in heat-stressed human subjects could explain the apparent increase in susceptibility to disease.

Abstract P210: Central Blockade Of Tumor Necrosis Factor-Á-Converting Enzyme (tace) Ameliorates Neuroinflammation, Sympathetic Excitation And Cardiac Dysfunction In Heart Failure Rat

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yang Yu ◽  
Baojian Xue ◽  
Hanzeng Li ◽  
Qing Chen ◽  
Mingxuan Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Cardiac Dysfunction ◽  
Tumor Necrosis ◽  
Left Ventricular ◽  
Male Rats ◽  
Tnf Α ◽  
Necrosis Factor

TACE is a key metalloprotease involved in ectodomain shedding of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-α. We previously reported that TACE-mediated production of TNF-α in the hypothalamic paraventricular nucleus (PVN) contributes to the sympathetic excitation in heart failure (HF). Additionally, the upregulated TGF-α in the PVN transactivates the epidermal growth factor receptor (EGFR) to activate extracellular signal-regulated kinase (ERK) 1/2 in HF. Here we sought to determine whether central inhibition of TACE attenuates neuroinflammation and prevents the progress of HF. Male rats underwent coronary artery ligation to induce HF or sham surgery (Sham). These rats were treated with bilateral PVN microinjection of a TACE siRNA or control siRNA while some rats received a 4-week intracerebroventricular (ICV) infusion of TACE inhibitor TAPI-0 or vehicle. Compared with Sham rats, HF rats treated with control siRNA, had higher (*P<0.05) levels of TNF-α (7.88±1.32* vs 2.77±0.98 pg/mL) and TGF-α (28.27±2.76* vs 11.62±2.48 pg/mL) in cerebrospinal fluid, and increased mRNA expression of TACE (2.53±0.30* vs 1.04±0.12), TNF-α (3.43±0.55* vs 1.03±0.11), TNF-α receptor 1 (2.32±0.27* vs 1.07±0.19), cyclooxygenase-2 (2.96±0.31* vs 1.10±0.19) and TGF-α (2.68±0.41* vs 1.06±0.14) in the PVN, but these levels were markedly reduced (39-54%*) in TACE siRNA-treated HF rats. Compared with control HF rats, HF rats treated with TACE siRNA had reduced expression of phosphorylated (p-) NF-κB p65 (1.27±0.14 vs 0.84±0.07*), p-EGFR (0.52±0.05 vs 0.37±0.04*) and p-ERK1/2 (1.06±0.10 vs 0.62±0.09*) in the PVN. Moreover, the elevated plasma norepinephrine levels, lung/body weight, heart/body weight and left ventricular (LV) end-diastolic pressure along with decreased LV dP/dt max in HF rats-treated with control siRNA were significantly attenuated in HF rats treated with TACE siRNA. Treatments with TACE siRNA in the PVN also improved the indicators of cardiac hypertrophy and fibrosis of HF. ICV infusion of TAPI-0 had the similar effects with PVN TACE siRNA on these variables in HF. These data indicate that central interventions suppressing TACE activity ameliorate neuroinflammation, sympathetic activation and cardiac dysfunction in HF.

scholarly journals A20 Inhibits NF-κB Activation in Endothelial Cells Without Sensitizing to Tumor Necrosis Factor–Mediated Apoptosis

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2249-2258 ◽  
Author(s):  
Christiane Ferran ◽  
Deborah M. Stroka ◽  
Anne Z. Badrichani ◽  
Jeffrey T. Cooper ◽  
Christopher J. Wrighton ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Inflammatory Stimuli ◽  
Protective Genes ◽  
The Mean ◽  
Induced Apoptosis ◽  
Therapeutic Perspective ◽  
Necrosis Factor ◽  
Inflammatory Effect

Expression of the NF-κB–dependent gene A20 in endothelial cells (EC) inhibits tumor necrosis factor (TNF)–mediated apoptosis in the presence of cycloheximide and acts upstream of IκBα degradation to block activation of NF-κB. Although inhibition of NF-κB by IκBα renders cells susceptible to TNF-induced apoptosis, we show that when A20 and IκBα are coexpressed, the effect of A20 predominates in that EC are rescued from TNF-mediated apoptosis. These findings place A20 in the category of “protective” genes that are induced in response to inflammatory stimuli to protect EC from unfettered activation and from undergoing apoptosis even when NF-κB is blocked. From a therapeutic perspective, genetic engineering of EC to express an NF-κB inhibitor such as A20 offers the mean of achieving an anti-inflammatory effect without sensitizing the cells to TNF-mediated apoptosis.

Comparisons of the Effects of Anesthesia and Stress on Release of Tumor Necrosis Factor-α, Leptin, and Nitric Oxide in Adult Male Rats

2001 ◽  
Vol 226 (4) ◽  
pp. 296-300 ◽  
Author(s):  
Claudio A. Mastronardi ◽  
Wen H. Yu ◽  
Samuel M. McCann
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Adult Male ◽  
Tumor Necrosis ◽  
Fold Increase ◽  
Male Rats ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Bacterial lipopolysaccharide (LPS) stimulates massive release of tumor necrosis factor-alpha (TNF-α) together with nitric oxide (NO) and a lessor release of leptin. We hypothesized that other types of stress such as that of surgery might also release these cytokines and NO. Adult male rats were anesthetized with ketamine/acepromazine/xylazine anesthesia (90 + 2 + 6 mg/ml, respectively) and an external jugular catheter was inserted for removal of blood samples (0.6 ml) at various times postoperatively. Plasma TNF-α was almost undetectable in decapitated rats and was near zero immediately following the placement of the jugular catheter (time zero [to]). As the rats awakened from anesthesia, there was a rise in TNF-α at 30 min that peaked at 2 hr with a 400-fold increase and then precipitously declined 40-fold to a level still greater than zero at 3 hr. At 6 hr on the following morning, TNF-α values were near zero, but following connection of tubing and withdrawal of the initial blood sample, there was a 100-fold increase 1 hr later, followed by a decline over the next 3 hr. In contrast, plasma [NO3/NO2] from decapitated rats was 117 μM. Values at t0 were decreased and plummeted 4-fold within 30 min, then rose slightly in the ensuing 3 hr. At 6 hr on the next day [NO3/NO2] values were lower than at t0 and declined gradually during the next 4 hr. Leptin gradually declined from pre-operative concentrations, reaching a minimum at 3 hr and its concentration was unaffected by the bleeding stress of the second day. We conclude that release of TNF-α, [NO3/NO2], and leptin are neurally controlled since plasma levels of all three declined as a result of anesthesia. TNF-α secretion was remarkably stress responsive, whereas NO release appeared to be suppressed by the combined operative and bleeding stress, and leptin was stress unresponsive.

Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy

1992 ◽  
Vol 263 (4) ◽  
pp. G579-G585 ◽  
Author(s):  
P. Akerman ◽  
P. Cote ◽  
S. Q. Yang ◽  
C. McClain ◽  
S. Nelson ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Tumor Necrosis ◽  
Thymidine Incorporation ◽  
Polyclonal Antibodies ◽  
Male Rats ◽  
Nuclear Antigen ◽  
Necrosis Factor Alpha ◽  
Necrosis Factor

Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by partial hepatectomy (PH) modulates the process of liver regeneration, adult male rats were injected intraperitoneally with either goat polyclonal antibodies to rat tumor necrosis factor (TNF; 15 micrograms/g body wt) or an equal amount of goat anti-rat immunoglobulin G 1 h before PH. Animals were killed at 12, 24, 48, or 72 h post-PH, 1 h after injection with [3H]thymidine. Serum TNF levels were measured with the L929 cytotoxicity assay, titers of antibody to TNF were determined by enzyme-linked immunoabsorbent assay, and interleukin-6 (IL-6) concentrations were measured by B9 cell bioassay. Liver regeneration was assessed by [3H]thymidine incorporation into hepatic DNA and by immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression. Antibodies to TNF were detected in treated rats but not in controls. Titers were highest at 12 h and progressively fell. Although TNF was never detected in serum, treatment with anti-TNF pre-PH significantly inhibited increases in serum IL-6 concentration post-PH. Anti-TNF pretreatment also inhibited [3H]thymidine incorporation into DNA, as well as expression of PCNA by both hepatocytes and liver nonparenchymal cells. These data indicate that TNF positively modulates liver regeneration after PH.

Effect of nutrition on tumor necrosis factor receptors in weight-gaining and -losing rats

1999 ◽  
Vol 277 (3) ◽  
pp. E464-E473 ◽  
Author(s):  
Nilima Raina ◽  
Jonathan Lamarre ◽  
Choong-Ching Liew ◽  
Amir H. Lofti ◽  
Khursheed N. Jeejeebhoy
Keyword(s):  
Plasma Membrane ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Energy Restriction ◽  
Male Rats ◽  
Northern Analysis ◽  
Cellular Expression ◽  
Protein Energy ◽  
Tnf Α ◽  
Necrosis Factor

Previous studies showed that weight-gaining rats had greater retention and reduced turnover of125I-labeled tumor necrosis factor (TNF)-α in the circulation compared with weight-losing animals. We therefore tested the hypothesis that protein-energy restriction with weight loss reduces the levels of soluble TNF-α receptor (sTNFR) and membrane TNFR (mTNFR) and the cellular expression of TNF-α mRNA. Twenty-six male rats weighing 200–220 g were fed a liquid formula diet for 10 days and divided equally into weight-gaining rats meeting all nutritional requirements (WG rats) and weight-losing rats with protein-energy restriction (WL rats).125I-TNF-α binding was demonstrated in plasma and plasma membrane to proteins of molecular masses of 92 and 243 kDa, a finding identical to that seen with purified human p55. Excess unlabeled TNF-α displaced the binding showing its specificity. The degree of binding to plasma protein and liver plasma membrane was markedly reduced in WL rats. Northern analysis showed that the expression of p55 mRNA was increased in the lungs and reduced in kidneys of WL compared with WG rats. The expression of p75 mRNA was not influenced by the nutritional status. We conclude that levels of sTNFR and mTNFR were reduced in WL rats. Reduced sTNFR and liver mTNFR are not due to a reduction in the expression of either p55 or p75 mRNA in WL rats. Reduced mTNFR, together with reduced shedding of soluble receptors, may have a protective role in WL rats.

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