The use of cytokines as indicators for drug safety

Abstract

In developing new compounds, questions about safety and efficacy are raised. Conventional preclinical studies of new compounds focus on bio-distribution, toxicology, safety pharmacology, pharmacokinetics, efficacy etc., but little information regarding the effect of these compounds on inflammatory cytokines are available. Cytokines can be used as markers to identify drug safety, focusing on cardiovascular, neurologic, and respiratory functions. Cytokines are produced by different cell groups, mainly by macrophages and helper T cells3 . Cytokines can be divided into two main groups: antiinflammatory cytokines and pro-inflammatory cytokines. Cytokines function as a complex network to control each other's responses and production4 . According to literature, a dysregulation of inflammatory markers or biomarkers can be indicative of chronic inflammation 1,2. There is no data available on the inflammatory cytokine values in healthy people and there is no formal reference of normal ranges of inflammatory markers. By establishing a baseline, it can be used in preclinical studies to determine the effects of new compounds on cytokines. The aim of this study is to determine baseline inflammatory cytokines concentration in an established in vivo model to eventually determine the effects of new radiolabeled compounds on the cytokines. Using an established xenograft model, a control baseline, a disease control (cancer), and drug treatment (radiopharmaceutical) cytokine levels will be determined by cytokine analyses of collected blood serum and tissues Antigenix America Inc.'s SUPER –X PLEX™ Flow Cytometry cytokine assays will be used on the BD Accuri® C6 Flow Cytometer. This multiplex assay has multiple bead populations, which are differentiated by the levels of fluorescence intensity and size. This allows for a distinct bead populations on the flow cytometer data output. It also makes it possible to measure multiple analytes with a single reaction. The following results are anticipated: Determining the individual baseline concentrations of the inflammatory cytokines. To observe a clear change in cytokine profiles between the baseline, disease control and drug treatmen