Preface

Cytokines have been a focus of scientific interest at least since the 1980's. Analyzing their expression patterns has permitted a better understanding of the pathogenesis of various diseases, including the inflammatory dermatoses. Exploring T-cell mediated skin diseases such as psoriasis, atopic dermatitis, and allergic contact dermatitis in this context is of particular interest since the skin is becoming increasingly recognized as a "visible immunological organ". These T-cell mediated diseases are characterized by abnormal cytokine expression patterns and can be considered as "model diseases" for other inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, organ transplant rejection, and inflammatory bowel disease.

Cytokines are now far beyond the stage when they were of interest only to the research sector as some cytokine-directed therapies are already being employed as part of the clinical practice. Strategies for neutralizing cytokines by using antibodies, fusion globulins, or soluble receptors have become available and have led to remarkable results in the clinic. Some of these new approaches currently under investigation have led already, or will likely lead shortly, to the registration of new drugs that will supplement existing therapeutic options for inflammatory skin diseases. In addition, the results of the clinical trials are contributing significantly to our understanding of the pathophysiology of diseases and will allow greater insight into which mechanisms play a significant role in their development. Thus, the clinical findings that neutralizing TNF-a is extremely effective in psoriasis, whereas neutralizing IL-8 is not, would suggest a much greater role for TNF-a in the pathogenesis of the disease. Recent research has also led to the discovery of novel cytokines in the expanding IL-1, IL-10, and IL-12 families and has provided insight into the molecular mechanisms of cytokine action, including discovery of novel signal transduction pathways. These investigations are leading to the identification of novel targets that, in contrast to the cytokines and their protein- based neutralizing therapies, may be amenable to inhibition by small molecules that are suitable for oral application. All of these developments may generate additional momentum for still better targeted pharmacological approaches.

To discuss these recent exciting developments we held the workshop: CYTOKINES AS POTENTIAL THERAPEUTIC TARGETS FOR INFLAMMATORY SKIN DISEASES, from November 17-19, 2004 in the beautiful environment of the Napa Valley, a short distance north of San Francisco. This meeting was intended to bring together an outstanding group of scientists spanning the broad scope of cytokine research and to have open discussions on recent achievements and future developments in the field. This aim was successfully achieved thanks to the generous support of the Ernst Schering Research Foundation and to the active contributions of the participants. We had the pleasure to host colleagues, who are experts in cytokine genetics, cytokine signaling and skin immunology. At this workshop, sessions comprised: i) Proinflam-matory cytokines beyond TNF as novel targets for psoriasis and other immune diseases - lessons from first clinical trials, ii) Modulation of cytokine expression by targeting APC, T-cells and their interactions, iii) Cytokines and their pathways as novel targets for immune diseases and, iv) Inhibition of cytokine signaling mechanisms. The proceedings of the workshop are contained in this volume and we wish to take this opportunity to thank the speakers and participants for their presentations and lively contributions. We trust that the readers will share with us our enthusiasm and continued excitement in the developments coming out of the field of cytokine research, which will open new avenues for the therapy of inflammatory skin diseases and other immune disorders.

Robert Numerof Charles A. Dinarello Khusru Asadullah

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Curing Eczema Naturally

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