scholarly journals Modulation of plasma cytokine levels in mice without and with collagen induced arthritis by CO2 and isofluorane.

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Lawrance Christopher ◽  
Heather Alexander ◽  
Stephen Clarke ◽  
Edralin Lucas ◽  
Brenda Smith ◽  
...  
Keyword(s):  
Collagen Induced Arthritis ◽  
Plasma Cytokine ◽  
Cytokine Levels

scholarly journals Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington’s Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

2021 ◽  
Author(s):  
Danielle A. Simmons ◽  
Brian D. Mills ◽  
Robert R. Butler III ◽  
Jason Kuan ◽  
Tyne L. M. McHugh ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Treatment Response ◽  
Diffusion Tensor ◽  
Disease Onset ◽  
Therapeutic Effects ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Pharmacodynamic Biomarkers

AbstractHuntington’s disease (HD) is caused by an expansion of the CAG repeat in the huntingtin gene leading to preferential neurodegeneration of the striatum. Disease-modifying treatments are not yet available to HD patients and their development would be facilitated by translatable pharmacodynamic biomarkers. Multi-modal magnetic resonance imaging (MRI) and plasma cytokines have been suggested as disease onset/progression biomarkers, but their ability to detect treatment efficacy is understudied. This study used the R6/2 mouse model of HD to assess if structural neuroimaging and biofluid assays can detect treatment response using as a prototype the small molecule p75NTR ligand LM11A-31, shown previously to reduce HD phenotypes in these mice. LM11A-31 alleviated volume reductions in multiple brain regions, including striatum, of vehicle-treated R6/2 mice relative to wild-types (WTs), as assessed with in vivo MRI. LM11A-31 also normalized changes in diffusion tensor imaging (DTI) metrics and diminished increases in certain plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6, in R6/2 mice. Finally, R6/2-vehicle mice had increased urinary levels of the p75NTR extracellular domain (ecd), a cleavage product released with pro-apoptotic ligand binding that detects the progression of other neurodegenerative diseases; LM11A-31 reduced this increase. These results are the first to show that urinary p75NTR-ecd levels are elevated in an HD mouse model and can be used to detect therapeutic effects. These data also indicate that multi-modal MRI and plasma cytokine levels may be effective pharmacodynamic biomarkers and that using combinations of these markers would be a viable and powerful option for clinical trials.

scholarly journals LGK974 suppresses lipopolysaccharide-induced endotoxemia in mice by modulating the crosstalk between the Wnt/β-catenin and NF-κB pathways

2021 ◽  
Vol 53 (3) ◽  
pp. 407-421
Author(s):  
Jaewoong Jang ◽  
Jaewon Song ◽  
Hyunji Lee ◽  
Inae Sim ◽  
Young V. Kwon ◽  
...  
Keyword(s):  
Animal Model ◽  
Survival Rate ◽  
Wnt Pathway ◽  
Cytokine Production ◽  
Cytokine Storm ◽  
Plasma Cytokine ◽  
Gram Negative ◽  
Multiple Organs ◽  
Expression Of Genes ◽  
Cytokine Levels

AbstractEndotoxemia, a type of sepsis caused by gram-negative bacterial endotoxin [i.e., lipopolysaccharide (LPS)], is associated with manifestations such as cytokine storm; failure of multiple organs, including the liver; and a high mortality rate. We investigated the effect and mechanism of action of LGK974, a Wnt signaling inhibitor, in mice with LPS-induced endotoxemia, an animal model of sepsis. LGK974 significantly and dose-dependently increased the survival rate and reduced plasma cytokine levels in mice with LPS-induced endotoxemia. Transcriptome analysis of liver tissues revealed significant changes in the expression of genes associated with the Wnt pathway as well as cytokine and NF-κB signaling during endotoxemia. LGK974 treatment suppressed the activation of NF-κB signaling and cytokine expression as well as the Wnt/β-catenin pathway in the livers of endotoxemic mice. Coimmunoprecipitation of phospho-IκB and β-transducin repeat-containing protein (β-TrCP) was increased in the livers of endotoxemic mice but was reduced by LGK974 treatment. Moreover, LGK974 treatment decreased the coimmunoprecipitation and colocalization of β-catenin and NF-κB, which were elevated in the livers of endotoxemic mice. Our results reveal crosstalk between the Wnt/β-catenin and NF-κB pathways via interactions between β-TrCP and phospho-IκB and between β-catenin and NF-κB during endotoxemia. The results of this study strongly suggest that the crosstalk between the Wnt/β-catenin and NF-κB pathways contributes to the mutual activation of these two pathways during endotoxemia, which results in amplified cytokine production, liver damage and death, and that LGK974 suppresses this vicious amplification cycle by reducing the crosstalk between these two pathways.

Plasma Cytokine Levels in Tanzanian HIV-1-Infected Adults and the Effect of Antiretroviral Treatment

2009 ◽  
Vol 52 (4) ◽  
pp. 493-497 ◽  
Author(s):  
Judith M Haissman ◽  
Lasse S Vestergaard ◽  
Samuel Sembuche ◽  
Christian Erikstrup ◽  
Bruno Mmbando ◽  
...  
Keyword(s):  
Antiretroviral Treatment ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Hiv 1

Plasma Cytokine Levels in Relation to Neuropsychiatric Symptoms and Cognitive Dysfunction in Huntington’s disease

2016 ◽  
Vol 5 (4) ◽  
pp. 369-377 ◽  
Author(s):  
Jos A. Bouwens ◽  
Erik van Duijn ◽  
Christa M. Cobbaert ◽  
Raymund A.C. Roos ◽  
Roos C. van der Mast ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Dysfunction ◽  
Neuropsychiatric Symptoms ◽  
Plasma Cytokine ◽  
Cytokine Levels

scholarly journals Lack of elevation in plasma levels of pro-inflammatory cytokines in common rodent models of pulmonary arterial hypertension: questions of construct validity for human patients

2017 ◽  
Vol 7 (2) ◽  
pp. 476-485 ◽  
Author(s):  
Kenny Schlosser ◽  
Mohamad Taha ◽  
Yupu Deng ◽  
Baohua Jiang ◽  
Lauralyn A McIntyre ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Animal Models ◽  
Arterial Hypertension ◽  
Inflammatory Cytokines ◽  
Plasma Levels ◽  
Rodent Models ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Pulmonary Arterial ◽  
Pro Inflammatory Cytokines

Translational research depends on the relevance of animal models and how well they replicate human disease. Here, we investigated plasma levels of three important pro-inflammatory cytokines (TNFα, IL-6, and MCP-1), known to be elevated in human pulmonary arterial hypertension (PAH), and systematically assessed their levels in PAH patients compared to five different rodent models of pulmonary hypertension (PH). A consistent immunoassay platform (Luminex xMAP) and source (Millipore) was used to measure all specimens. PAH patients (n = 29) exhibited significant elevations in all three cytokines (median [IQR] pg/mL; TNFα, 7.0 [4.8–11.7]; IL-6, 9.2 [3.8–17.2]; MCP-1, 109 [65–142]) versus healthy participants (n = 20) (median [IQR] pg/mL; TNFα, 3.0 [2.0–3.6]; IL-6, 1.7 [0.5–7.2]; MCP-1, 79 [49–93]. In contrast, mice with PH established after three weeks of hypoxia (n = 18) or SU5416 plus hypoxia (n = 20) showed no significant change in their plasma cytokine levels versus controls (n = 16), based on three to four independent experiments per group. Similarly, plasma cytokine levels were not elevated in rats with PH established three weeks after monocrotaline (n = 23), eight weeks after SU5416 alone (n = 10) or six to eight weeks after SU5416 plus hypoxia (n = 21) versus controls (n = 36 rats), based on three to eight independent experiments per group. Positive biologic control specimens from sepsis patients (n = 9), cecal-ligation and puncture (CLP)-induced septic mice (n = 6), and lipopolysaccharide-induced septic rats (n = 4) showed robust elevations in all three cytokines. This study suggests that animal models commonly used for the development of novel diagnostic and therapeutic approaches for PAH may have limited construct validity with respect to markers of systemic immune activation seen in human patients.

Plasma cytokine levels in patients with chronic alcohol overconsumption: Relations to gut microbiota markers and clinical correlates

Alcohol ◽  
2020 ◽  
Vol 85 ◽  
pp. 35-40 ◽  
Author(s):  
Steinar Traae Bjørkhaug ◽  
Sudan Prasad Neupane ◽  
Jørgen G. Bramness ◽  
Håvard Aanes ◽  
Viggo Skar ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Chronic Alcohol ◽  
Plasma Cytokine ◽  
Clinical Correlates ◽  
Cytokine Levels
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