ReviewToxicological sciences : an official journal of the Society of Toxicology2010
Blood cytokines as biomarkers of in vivo toxicity in preclinical safety assessment: considerations for their use.
Review in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 136 citations in OpenAlex.
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- In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo.Nature communications · 2020Article
- The endogenous capacity to produce proinflammatory mediators by the ex vivo human perfused lung.Intensive care medicine experimental · 2020Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.