A Comparative Analysis of Acute-phase Proteins as Inflammatory Biomarkers in Preclinical Toxicology Studies: Implications for Preclinical to Clinical Translation

• Published in: Toxicologic pathology Vol. 37; no. 1; pp. 28 - 33
• Main Authors: Watterson, Claire, Lanevschi, Anne, Horner, Judith, Louden, Calvert
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-01-2009; Sage Publications
• Subjects: Acute-Phase Proteins - metabolism; Animals; Biological and medical sciences; Biomarkers - metabolism; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Humans; Medical sciences; Mice; Rats; Systemic Inflammatory Response Syndrome - chemically induced; Systemic Inflammatory Response Syndrome - diagnosis; Systemic Inflammatory Response Syndrome - metabolism; Toxicity Tests - methods; Toxicology; Xenobiotics - toxicity; preclinical safety assessment—risk management; inflammation; biomarkers; Acute phase protein; Toxicology; preclinical safety assessment-risk management; Toxicity; Preclinical trial; Biological marker; Inflammation; Risk management; Genetic translation; Comparative study
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1177/0192623308329286

Recently, in early clinical development, a few biologics and small molecules intended as antitumor or anti-inflammatory agents have caused a severe adverse pro-inflammatory systemic reaction also known as systemic inflammatory response syndrome (SIRS). This toxicity could result from expected pharmacological effects of a therapeutic antibody and/or from interaction with antigens expressed on cells/tissues other than the intended target. Clinical monitoring of SIRS is challenging because of the narrow diagnostic window to institute a successful intervening therapeutic strategy prior to acute circulatory collapse. Furthermore, for these classes of therapeutic agents, studies in animals have low predictive ability to identify potential human hazards. In vitro screens with human cells, though promising, need further development. Therefore, identification of improved preclinical diagnostic markers of SIRS will enable clinicians to select applicable markers for clinical testing and avoid potentially catastrophic events. There is limited preclinical toxicology data describing the interspecies performance of acute-phase proteins because the response time, type, and duration of major acute-phase proteins vary significantly between species. This review will attempt to address this intellectual gap, as well as the use and applicability of acute-phase proteins as preclinical to clinical translational biomarkers of SIRS.