No association between tumor necrosis factor-α production and gene polymorphisms among inbred rat strains

Warlé, Michiel C.; Laan, Luc J. W. van der; Kusters, Johannes G.; Pot, Raymond G.J.; Hop, Wim C. J.; Segeren, Katja C. A.; IJzermans, Jan N.M.; Metselaar, Herold J.; Tilanus, Hugo W.

doi:10.1016/j.trim.2005.04.002

Cited by 1 publication

(2 citation statements)

References 18 publications

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“…Cytokine gene polymorphisms in preclinical toxicity species are not well described. An investigation comparing polymorphisms in the regulatory regions of the rat TNF-α gene and in vitro TNF-α release to splenocyte stimulation failed to show a relationship (Warle et al , 2005). Cytokine genes also have different conservation across species.…”

Section: Considerations Related To Cytokine Biologymentioning

confidence: 99%

“…The strain resistance variation of mice to bleomycin-induced pulmonary fibrosis is attributable in part to differences in the induction of cytokine receptor expression in the lung (Cavarra et al , 2004). A log-fold difference in TNF-α production in response to in vitro splenocyte stimulation has been demonstrated between rat strains (Warle et al , 2005). The availability of reagents has allowed characterization of many of the wide ranging differences between human and mouse immune systems that impact cytokine expression.…”

Section: The Influence Of Preclinical Toxicity Study Factors On Cytokmentioning

confidence: 99%

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Blood Cytokines as Biomarkers of In Vivo Toxicity in Preclinical Safety Assessment: Considerations for Their Use

Tarrant¹

2010

Toxicological Sciences

116

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In the drive to develop drugs with well-characterized and clinically monitorable safety profiles, there is incentive to expand the repertoire of safety biomarkers for toxicities without routine markers or premonitory detection. Biomarkers in blood are pursued because of specimen accessibility, opportunity for serial monitoring, quantitative measurement, and the availability of assay platforms. Cytokines, chemokines, and growth factors (here referred to collectively as cytokines) show robust modulation in proximal events of inflammation, immune response, and repair. These are key general processes in many toxicities; therefore, cytokines are commonly identified during biomarker discovery studies. In addition, multiplexed cytokine immunoassays are easily applied to biomarker discovery and routine toxicity studies to measure blood cytokines. However, cytokines pose several challenges as safety biomarkers because of a short serum half-life; low to undetectable baseline levels; lack of tissue-specific or toxicity-specific expression; complexities related to cytokine expression with multiorgan involvement; and species, strain, and interindividual differences. Additional challenges to their application are caused by analytical, methodological, and study design–related variables. A final consideration is the strength of the relationship between changes in cytokine levels and the development of phenotypic or functional manifestations of toxicity. These factors should inform the integrated judgment-based qualification of novel biomarkers in preclinical, and potentially clinical, risk assessment. The dearth of robust, predictive cytokine biomarkers for specific toxicities is an indication of the significant complexity of these challenges. This review will consider the current state of the science and recommendations for appropriate application of cytokines in preclinical safety assessment.

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Section: Considerations Related To Cytokine Biologymentioning

confidence: 99%

Section: The Influence Of Preclinical Toxicity Study Factors On Cytokmentioning

confidence: 99%

Blood Cytokines as Biomarkers of In Vivo Toxicity in Preclinical Safety Assessment: Considerations for Their Use

Tarrant¹

2010

Toxicological Sciences

116

View full text Add to dashboard Cite

show abstract

No association between tumor necrosis factor-α production and gene polymorphisms among inbred rat strains

Cited by 1 publication

References 18 publications

Blood Cytokines as Biomarkers of In Vivo Toxicity in Preclinical Safety Assessment: Considerations for Their Use

Blood Cytokines as Biomarkers of In Vivo Toxicity in Preclinical Safety Assessment: Considerations for Their Use

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