Sanne Hoeks

Chapter 6 82 antibody agonist TGN1412 resulted in a severe cytokine storm in healthy volunteers. 10, 11 These positive and negative cytokine mediated events illustrate that cytokines are key components of effector phase immunity. Thus, monitoring these molecules can provide key insight into disease progression or regression, in essence, cytokines can be looked at as biomarkers of a disease process. Per definition, biomarkers are ‘‘A characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention’’. 12 Biomarkers can be discovered and isolated locally (biopsies) or systemically (e.g. blood or urine) and can either be drug- related or disease-related with cytokines falling into the latter of these categories. Disease related biomarkers provide insight into the possible effect of treatment on a patient (predictive marker), the disease state of a patient (diagnostic marker) or future disease development with regards to a certain outcome but irrespective of treatment (prognostic marker). 13 In order for cytokines to take on this biomarker role however, a key hurdle needs to be overcome, namely that of a lack of standardization in cytokine analysis. This standardization process is independent of cytokine structure or biology but dependent on protocols and sample handling. This review aims to provide a comprehensive overview on current methods for cytokine analysis in an effort to provide a means to standardization that will be applicable to biomarker discovery and validation in a clinical context. Chemokine concentration Activation & differentiation autocrine paracrine Migration endocrine juxtacrine Chemokines Interleukins Figure-1 FIGURE 1. General function of cytokines. When secreted cytokines (interleukins) can act on cells or tissue that secrete them (autocrine), surrounds them (paracrine), travel to distant cells (endocrine) or remain cell bound and activate neighboring cells (juxtacrine). On the other hand chemokines are regulatory proteins which induce migration, activation and differentiation of cells to inflamed or damaged tissue.