Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice

1999 ◽  
Vol 276 (1) ◽  
pp. R52-R58 ◽  
Author(s):  
Lada Paul ◽  
Vadim Fraifeld ◽  
Jacob Kaplanski
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Ex Vivo ◽  
Induced Hypothermia ◽  
Significant Elevation ◽  
Hypothermic Effect ◽  
Tnf Α ◽  
Α Level ◽  
Factor Α ◽  
Necrosis Factor

The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (Tb) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in Tb, plasma tumor necrosis factor-α (TNF-α), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 μg/mouse) led to a decrease in Tb starting 1 h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF-α level in plasma and in LT and PGE2 production by ex vivo-incubated hypothalamus. MK-886 (1 mg/kg ip) administered 4 h before LPS efficaciously prevented LPS-induced hypothermia in mice. Pretreatment of mice with MK-886 did not alter the LPS-stimulated increase in plasma TNF-α. MK-886 significantly inhibited LT and enhanced PGE2 production in hypothalamus compared with LPS alone. These results suggest that 1) LPS-induced hypothermia may be mediated by LTs and 2) the antihypothermic effect of MK-886 is not associated with TNF-α bioactivity.

The change of proinflammatory cytokine tumor necrosis factor α level in the use of meloxicam in rat model of osteoarthritis

2019 ◽  
Vol 30 (6) ◽  
Author(s):  
Junaidi Khotib ◽  
Naning Windi Utami ◽  
Maria Apriliani Gani ◽  
Chrismawan Ardianto
Keyword(s):  
Tumor Necrosis Factor ◽  
Rat Model ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Control Group ◽  
Treatment Groups ◽  
Tnf Α ◽  
Α Level ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background Osteoarthritis (OA) is a chronic disease in the joints. One of the proinflammatory cytokines that is thought to have a major role in the inflammatory process, the emergence of pain, and cartilage damage in OA is tumor necrosis factor α (TNF-α). Meloxicam is a nonsteroidal anti-inflammatory drug class of drugs that is relatively selective in inhibiting the activity of cyclooxygenase 2 (COX-2) formation. This study is conducted to prove the change in TNF-α level in the use of meloxicam with model in animals suffering from OA. Methods The OA rat model was induced with sodium monoiodoacetate intra-articularly. Rats were divided into 5 groups: negative control group, positive control group, and treatment groups with various doses of meloxicam. Hyperalgesia effect was evaluated using a warm plate test, and TNF-α level was determined using enzyme-linked immunosorbent assay. Results The treatment groups that received meloxicam at a dose of 1.0, 3.0, or 10.0 mg/kg body weight (BW) did not show significant differences in rat knee joint diameter (p = 0.99), but showed a significant difference in sensitivity to heat stimulation (p = 0.02) compared to the control group. Osteoarthritis rats experienced a significant reduction in TNF-α level after being given meloxicam at a dose of 10 mg/kg BW compared with the control group. This shows that the 10 mg/kg BW of meloxicam is a potential dose in reducing the TNF-α level in OA rat models. Conclusions Based on these data, it can be concluded that the inhibition of pain and the development of OA by meloxicam in animal models may be assigned to a decreased level of TNF-α.

scholarly journals The clinical significance of tumor necrosis factor-α plasma level in patients having chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1215-1219 ◽  
Author(s):  
Alessandra Ferrajoli ◽  
Michael J. Keating ◽  
Taghi Manshouri ◽  
Francis J. Giles ◽  
Amanda Dey ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Lymphocytic Leukemia ◽  
Tnf Α ◽  
The Mean ◽  
Α Level ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor-α (TNF-α), a cytokine possessing pleiotropic biological activities, is produced by leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL) and acts as an autocrine and paracrine growth factor in this disease. In this study, TNF-α levels were determined in 150 patients with CLL and correlated with disease characteristics, prognostic factors, and survival. The mean TNF-α plasma concentration in the patients with CLL was significantly higher than in the healthy control population (16.4 versus 8.7 pg/mL; P < .0001). Patients having an elevated TNF-α level had more advanced Rai and Binet stage disease, higher serum β2-microglobulin (β2M) levels, a greater percentage of cells expressing CD38, and lower hemoglobin and platelet levels. Patients having chromosomal abnormalities such as 11q deletion, trisomy 12, and chromosome 17 aberrations had a higher mean TNF-α level (27.5 pg/mL) than patients having a diploid karyotype or other miscellaneous cytogenetic abnormalities (14.2 pg/mL;P < .001). The TNF-α level was a predictor of survival when the Cox proportional hazards model was used with TNF-α entered as a continuous variable (P = .0001). Also, patients having a TNF-α level above the mean value of 14 pg/mL had significantly shorter survival duration (P = .00001). The TNF-α level remained predictive of survival in Cox multivariate analysis independent of Rai staging and β2M, hemoglobin, prior therapy, white cell count, and platelet level (P = .005). We conclude that the TNF-α level serves as a prognostic factor in patients with CLL and that inhibition of TNF-α in these patients could have therapeutic importance.

scholarly journals Association between tumor necrosis factor-α and chronic obstructive pulmonary disease: a systematic review and meta-analysis

2019 ◽  
Vol 13 ◽  
pp. 175346661986609 ◽  
Author(s):  
Yang Yao ◽  
Jing Zhou ◽  
Xin Diao ◽  
Shengyu Wang
Keyword(s):  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Meta Analysis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Tnf Α ◽  
Α Level ◽  
Factor Α ◽  
Necrosis Factor

Background: Patients diagnosed with chronic obstructive pulmonary disease (COPD) have increased risks for a series of physical and mental illnesses. Tumor necrosis factor-α (TNF-α) has been reported to participate in the development of COPD and its complications. However, the values of blood TNF-α level used in the diagnosis of COPD remains controversial. In view of this, we performed a systematic review and meta-analysis to evaluate the correlation between TNF-α level and COPD. Methods: We searched PubMed, Web of Science, Embase and CNKI up to May 2018. The selection criteria were set according to the PICOS framework. A random-effects model was then applied to evaluate the overall effect sizes by calculating standard mean difference (SMD) and its 95% confidence intervals (CIs). Results: A total of 40 articles containing 4189 COPD patients and 1676 healthy controls were included in this meta-analysis. The results indicated a significant increase in TNF-α level in the COPD group compared with the control group (SMD: 1.24, 95% CI: 0.78–1.71, p < 0.00001). According to the subgroup analyses, we noted that TNF-α level was associated with predicted first second of forced expiration (FEV1) (%) and study region. However, no association between TNF-α level and COPD was found when the participants were nonsmokers, and the mean age was less than 60 years. Conclusions: Our results indicated that TNF-α level was increased in COPD patients when compared with healthy controls. Illness progression and a diagnosis of COPD might contribute to higher TNF-α levels. However, the underlying mechanism still remains unknown and needs further investigation. The reviews of this paper are available via the supplemental material section.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor α Inhibition for Alzheimer’s Disease

2017 ◽  
Vol 9 ◽  
pp. 117957351770927 ◽  
Author(s):  
Rudy Chang ◽  
Kei-Lwun Yee ◽  
Rachita K Sumbria
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Short Review ◽  
Tnf Α ◽  
Factor Α ◽  
Ad Therapy ◽  
Necrosis Factor

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

Tumor necrosis factor-α-associated lysosomal permeabilization is cathepsin B dependent

2002 ◽  
Vol 283 (4) ◽  
pp. G947-G956 ◽  
Author(s):  
Nathan W. Werneburg ◽  
M. Eugenia Guicciardi ◽  
Steven F. Bronk ◽  
Gregory J. Gores
Keyword(s):  
Tumor Necrosis Factor ◽  
Cathepsin B ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Fluorescent Protein ◽  
Tnf Α ◽  
Calcein Release ◽  
Green Fluorescent ◽  
Factor Α ◽  
Necrosis Factor

Cathepsin B (Cat B) is released from lysososomes during tumor necrosis factor-α (TNF-α) cytotoxic signaling in hepatocytes and contributes to cell death. Sphingosine has recently been implicated in lysosomal permeabilization and is increased in the liver by TNF-α. Thus the aims of this study were to examine the mechanisms involved in TNF-α-associated lysosomal permeabilization, especially the role of sphingosine. Confocal microscopy demonstrated Cat B-green fluorescent protein and LysoTracker Red were both released from lysosomes after treatment of McNtcp.24 cells with TNF-α/actinomycin D, a finding compatible with lysosomal destabilization. In contrast, endosomes labeled with Texas Red dextran remained intact, suggesting lysosomes were specifically targeted for permeabilization. LysoTracker Red was released from lysosomes in hepatocytes treated with TNF-α or sphingosine in Cat B(+/+) but not Cat B(−/−) hepatocytes, as assessed by a fluorescence-based assay. With the use of a calcein release assay in isolated lysosomes, sphingosine permeabilized liver lysosomes isolated from Cat B(+/+) but not Cat B(−/−) liver. C6ceramide did not permeabilize lysosomes. In conclusion, these data implicate a sphingosine-Cat B interaction inducing lysosomal destabilization during TNF-α cytotoxic signaling.

Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis

2009 ◽  
Vol 36 (4) ◽  
pp. 837-842 ◽  
Author(s):  
ANA FILIPA MOURÃO ◽  
JOANA CAETANO-LOPES ◽  
PAULA COSTA ◽  
HELENA CANHÃO ◽  
MARIA JOSÉ SANTOS ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Inflammatory Activity ◽  
Serum Concentrations ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Objective.Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes.Methods.Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism.Results.One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype.Conclusion.TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.

scholarly journals Tumor Necrosis Factor α Regulates Responses to Nerve Growth Factor, Promoting Neural Cell Survival but Suppressing Differentiation of Neuroblastoma Cells

2008 ◽  
Vol 19 (3) ◽  
pp. 855-864 ◽  
Author(s):  
Yoshinori Takei ◽  
Ronald Laskey
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Neuroblastoma Cells ◽  
Erk Activation ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Although nerve growth factor (NGF) promotes survival of neurons, tumor necrosis factor α (TNF-α) contributes to cell death triggered by NGF depletion, through TNF-α receptor (TNFR) 1. In contrast to this effect, TNF-α can promote neural cell survival via TNF-α receptor TNFR2. Although these findings demonstrate pivotal roles of TNF-α and NGF in cell fate decisions, cross-talk between these signaling pathways has not been clarified. We find that NGF can induce TNF-α synthesis through the nuclear factor-κB transcription factor. This provides a new basis for examining the cross-talk between NGF and TNF-α. Inhibition of TNFR2 shows opposite effects on two downstream kinases of NGF, extracellular signal-regulated kinase (Erk) and Akt. It increases Erk activation by NGF, and this increased activation induces differentiation of neuroblastoma cell lines. Reciprocally, inhibition of TNFR2 decreases Akt activation by NGF. Consistent with an essential role of Akt in survival signaling, inhibition of TNF-α signaling decreases NGF-dependent survival of neurons from rat dorsal root ganglia. Thus, NGF and NGF-induced TNF-α cooperate to activate Akt, promoting survival of normal neural cells. However, the NGF-induced TNF-α suppresses Erk activation by NGF, blocking NGF-induced differentiation of neuroblastoma cells. TNFR2 signaling could be a novel target to modulate cell responses to NGF.

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