scholarly journals The Effects of a Novel Inhibitor of Tumor Necrosis Factor (TNF) Alpha on Prepulse Inhibition and Microglial Activation in Two Distinct Rodent Models of Schizophrenia

2019 ◽  
Author(s):  
Heath W. Shelton ◽  
Somasundar Prasad Gabbita ◽  
W. Drew Gill ◽  
Katherine C. Burgess ◽  
Wyatt S. Whicker ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Necrosis Factor ◽  
Prepulse Inhibition ◽  
Tumor Necrosis ◽  
Microglial Activation ◽  
Sensorimotor Gating ◽  
Poly I:C ◽  
Rodent Models ◽  
Dopamine D2 ◽  
Necrosis Factor

Abstract Background: Increased neuroinflammation has been shown in individuals diagnosed with schizophrenia (SCHZ). This study evaluated a novel immune modulator (PD2024) that targets the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) to alleviate sensorimotor gating deficits and microglial activation employing two different rodent models of SCHZ. Methods: In Experiment 1, rats were neonatally treated with saline or the dopamine D2-like agonist quinpirole (NQ; 1 mg/kg) from postnatal day (P) 1-21 which produces increases of dopamine D2 receptor sensitivity throughout the animal’s lifetime. In Experiment 2, rats were neonatally treated with saline or the immune system stimulant polyinosinic:polycytidylic acid (Poly I:C) from P5-7. Neonatal Poly I:C treatment mimics immune system activation associated with SCHZ. In both experiments, rats were raised to P30 and administered a control diet or a novel TNFα inhibitor PD2024 (10mg/kg) in the diet from P30 until P67. At P45-46 and from P60-67, animals were behaviorally tested on auditory sensorimotor gating as measured through prepulse inhibition (PPI). Results: NQ or Poly I:C treatment resulted in PPI deficits, and PD2024 treatment alleviated PPI deficits in both models. Results also revealed that hippocampal microglial activation produced by neonatal Poly I:C was significantly reduced to control levels by PD2024. In addition, a separate group of animals neonatally treated with saline or Poly I:C from P5-7 demonstrated increased TNFα protein levels in the hippocampus, verifying increased TNFα in the brain produced by Poly I:C. Conclusions: Results from this study suggests that that brain TNFα is a viable pharmacological target to treat the neuroinflammation known to be associated with SCHZ.

scholarly journals The effects of a novel inhibitor of tumor necrosis factor (TNF) alpha on prepulse inhibition and microglial activation in two distinct rodent models of schizophrenia

2021 ◽  
Vol 406 ◽  
pp. 113229
Author(s):  
Heath W. Shelton ◽  
S. Prasad Gabbita ◽  
W. Drew Gill ◽  
Katherine C. Burgess ◽  
Wyatt S. Whicker ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Prepulse Inhibition ◽  
Tumor Necrosis ◽  
Microglial Activation ◽  
Tnf Alpha ◽  
Rodent Models ◽  
Necrosis Factor

Neopterin, soluble receptors for interleukin-2 and tumor necrosis factor in viral cirrhosis and alcoholic cirrhosis

Pteridines ◽  
2000 ◽  
Vol 11 (2) ◽  
pp. 43-47 ◽  
Author(s):  
Jorge Gonzalez-Calvin ◽  
Gernot P. Tilz ◽  
Francisco Gallego-Rojo ◽  
Marina Torres-Almendros ◽  
Bernhard Widner ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Immune System ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Alcoholic Cirrhosis ◽  
Serum Concentrations ◽  
Soluble Receptors ◽  
Cell Functions ◽  
Necrosis Factor

AbstractAlcoholic cirrhosis and viral cirrhosis are associated with alterations of immune system function and cytokine production. Our aim was to investigate whether serum concentrations of soluble receptors for interleukin-2 (sIL- 2 R) and tumor necrosis factor (55kD-type, sTNFR-55), and serum neopterin can be used as markers to establish differences in etiology and severity in liver cirrhosis and to determine whether they correlate with laboratory and clinical parameters. Thirty three patients with alcoholic and 15 with viral cirrhosis (classified according to the Child-Pugh score of severity of liver disease) and 43 healthy controls were studied. Serum concentrations of sIL2-R, sTNFR-55 and neopterin were significantly raised in patients. No significant differences between alcoholic and viral cirrhosis were found. The concentrations of sIL-2 Rand sTNFR-55 were significantly higher in patients with more severe disease. There existed correlations b<!tween sIL-2R and sTNFR-55 (rs = 0.50, P < 0.001) and between both soluble receptors and the Child-Pugh score (sTNF-R55: rs = 0.70, p < 0.001; sIL-2R: rs = 0.33, p < 0.05) and serum albumin. The results are likely to reflect that the monocyte-macrophage and T-cell functions are stimulated in patients with liver cirrhosis independently of the etiology of the disease, and the persistent activation of the immune system occurs in cirrhosis even at the end stage of the disease. Chronic immune activation might have deletereous consequences on the evolution of cirrhosis.

scholarly journals Immunomodulatory Activities of Sambucus javanica Extracts in DMBAExposedBALB/c Mouse

2019 ◽  
Vol 9 (4) ◽  
pp. 619-623
Author(s):  
Wira Eka Putra ◽  
Muhaimin Rifa'i
Keyword(s):  
Immune System ◽  
Tumor Necrosis Factor ◽  
Interferon Gamma ◽  
Broad Spectrum ◽  
Tumor Necrosis ◽  
Treated Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Purpose: Accumulating evidence shows the genus of Sambucus exerts a broad spectrum ofmedicinal potencies such as anticancer, antiviral, antibacterial, and antidiabetes. Based on theprevious studies, we hypothesized that bioactive compounds of Sambucus might alter severalbiological systems, including the immune system. Therefore, this study extensively aimed toevaluate the immunomodulatory activities of Sambucus javanica extracts in 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/c mouse.Methods: The experimental mice were orally administrated with 2.8 mg.kg-1 BW of DMBA forten times within a month. After that, the mice were treated by S. javanica berries and leavesextracts for 2 weeks. Subsequently, the inflammation rate was evaluated by using flow cytometryanalysis, whereas the necrosis incidences were observed by hematoxylin & eosin staining.Results: Based on the results, we found the expression of tumor necrosis factor alpha (TNF-α)and interferon gamma (IFN-ɣ) were increased however after treated by S. javanica berries andleaves extracts were significantly decreased. In the same way, necrosis incidence was increasedin the DMBA-treated group however it was diminished with S. javanica extracts treatment.Conclusion: Together, these results suggested that S. javanica extracts have immunomodulatoryactivities to suppress inflammation and reduce necrosis incidence in experimental mice.<br />

scholarly journals Inhibition of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension

2012 ◽  
Vol 209 (11) ◽  
pp. 1919-1935 ◽  
Author(s):  
Abdul G. Hameed ◽  
Nadine D. Arnold ◽  
Janet Chamberlain ◽  
Josephine A. Pickworth ◽  
Claudia Paiva ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Vascular Remodeling ◽  
Tumor Necrosis ◽  
Pulmonary Arteries ◽  
Systemic Circulation ◽  
Vascular Lesions ◽  
Rodent Models ◽  
Antibody Treatment ◽  
Pulmonary Vascular Remodeling ◽  
Necrosis Factor

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the progressive narrowing and occlusion of small pulmonary arteries. Current therapies fail to fully reverse this vascular remodeling. Identifying key pathways in disease pathogenesis is therefore required for the development of new-targeted therapeutics. We have previously reported tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) immunoreactivity within pulmonary vascular lesions from patients with idiopathic PAH and animal models. Because TRAIL can induce both endothelial cell apoptosis and smooth muscle cell proliferation in the systemic circulation, we hypothesized that TRAIL is an important mediator in the pathogenesis of PAH. We demonstrate for the first time that TRAIL is a potent stimulus for pulmonary vascular remodeling in human cells and rodent models. Furthermore, antibody blockade or genetic deletion of TRAIL prevents the development of PAH in three independent rodent models. Finally, anti-TRAIL antibody treatment of rodents with established PAH reverses pulmonary vascular remodeling by reducing proliferation and inducing apoptosis, improves hemodynamic indices, and significantly increases survival. These preclinical investigations are the first to demonstrate the importance of TRAIL in PAH pathogenesis and highlight its potential as a novel therapeutic target to direct future translational therapies.

scholarly journals Peripheral immune system suppression in early abstinent alcohol-dependent individuals: Links to stress and cue-related craving

2017 ◽  
Vol 31 (7) ◽  
pp. 883-892 ◽  
Author(s):  
Helen C Fox ◽  
Verica Milivojevic ◽  
Gustavo A Angarita ◽  
Raymond Stowe ◽  
Rajita Sinha
Keyword(s):  
Immune System ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Negative Mood ◽  
Alcohol Group ◽  
Alcohol Craving ◽  
Peripheral Immune System ◽  
Time Points ◽  
Necrosis Factor ◽  
Alcohol Dependent

Background: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. Methods: A total of 39 early abstinent, treatment-seeking, alcohol-dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. Results: The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also showed a dampened TNFα and TNFR1 response to stress and cue, respectively, and a generalized suppression of IL-6. In the alcohol group, these immune system adaptations occurred alongside significant elevations in anxiety, negative mood and alcohol craving. Conclusions: Findings demonstrate that broad immunosuppression is still observed in alcohol-dependent individuals after 3 weeks of abstinence and may be linked to motivation for alcohol.

Tumor necrosis factor–α promotes survival and phenotypic maturation of poly(I:C)-treated dendritic cells but impairs their Th1 and Th17 polarizing capability

Cytotherapy ◽  
2015 ◽  
Vol 17 (5) ◽  
pp. 633-646 ◽  
Author(s):  
Ana Thorne ◽  
Sergej Tomić ◽  
Bojan Pavlović ◽  
Dušan Mihajlović ◽  
Tanja Džopalić ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Poly I:C ◽  
Factor Α ◽  
Necrosis Factor
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