Review of Tissue-Protective Cytokines

mation having made many contributions to interleukin-1 (IL-1) and TNF. For example, Ghezzi was the first to report that hypoxia induced IL-1β and TNFα. In addition to their own chapters, the invited contributions are easy to read and each addresses a different aspect of this growing field of investigation. Driving the field are the clinical trials of EPO in patients with cerebral vascular accidents (stroke) and acute myocardial infarction, in which a benefit was reported. New clinical trials are presently underway. Experimental autoimmune encephalomyelitis (EAE) is the well established model for the human disease Multiple Sclerosis. The therapeutic benefit of EPO in this model is well-described in a chapter by Cerevellini, Ghezzi, and Mengozzi. It seems that this disease as well as ALS are ideally suited for EPO testing. The chapters provide clear information for both the novice entering the field or the investigator who studies mechanisms of cell death. Needless to write, the book is highly useful to the field of neurodegeneration. The first chapter by Brines and Cerami on the structure-function relationships of the unique, alternate EPO receptor is well written with clear diagrams showing the domains of the heterodimeric EPO receptor that triggers the protective pathway. Other chapters include explanations on EPO and non-EPP tissue targets, the structural basis for other tissue-protective cytokines and the properties of IL-6 as a regenerative cytokine. The chapter on IL-6 is highly relevant as this cytokine, often regarded as a pro-inflammatory cytokine, is often a protective cytokine. Galun and Stefan-Rose-John present their Tissue-Protective Cytokines is an up-to-date collection of articles edited by Pietro Ghezzi and Anthony Cerami (1). These editors are the leaders in the field, primarily with their pioneering studies on the ability of erythropoietin (EPO) to protect from cell death. The book is unique in many ways. Many chapters (19 Chapters) contain detailed methods and protocols for the experimental models, particularly in the brain and nervous system. This is an added benefit to the book because it helps the reader understand the models being used to evaluate the mechanism as well as the efficacy of tissue-protective cytokines that are being considered for therapies in various diseases. Most of the chapters review published studies or present new data on the properties and mechanism of action of EPO. As written in the Preface by Cerami, the EPO story starts with well know clinical observation in hemodialysis patients being treated with EPO for low level of hemoglobin. The patients, weak from years of low hemoglobin, feel better much faster and time-wise significantly before there is any increase in red blood cell mass. This suggested that EPO possessed another property. This observation encouraged Cerami, Ghezzi, and their collaborators to look carefully for the effect of EPO in animal models of inflammation. As pointed out in the Preface, Cerami’s studies on the tissue-protective properties of EPO led to the development of novel small molecules that do not stimulate erythropoiesis but rather protect against loss of cell function. The long-term collaboration of Ghezzi and Cerami on the inflammatory properties of tumor necrosis factor (TNFα) allowed for a new collaboration focused on the nonerythrogenic properties of EPO. Ghezzi is a Review of tissue-protective cytokines