Editorial [ Therapeutic Modulation of Prostanoids and Cytokines in Chronic Diseases Executive Editor: Anna Dongari-Bagtzoglou ]

Prostanoids and cytokines are secreted or cell-surface associated effector molecules, which mediate cell-to-cell communication and regulate complex biological processes in health and disease. Some of these molecules are synthesized by cells having highly specialized functions (such as cells of the endocrine system), but most are ubiquitously expressed in more than one cell type or tissue. Originally, such regulatory molecules involved in inflammation or immunity were termed cytokines, as opposed to mediators of cell growth and movement, which were named growth factors and chemokines, respectively. Today this distinction does not exist as all these "functional" categories essentially fall into one large family of cytokines. More than 100 cytokines with quite divergent functions are now characterized. As human life expectancy has risen in the last decades, due to advances in medicine, the prevalence of chronic, inflammatory, debilitating diseases of infectious or autoimmune origin has risen as well. Recently, inflammatory cytokines have been shown to play a central regulatory role not only in infection and immunity, but also in carcinogenesis, transplantation and other more common chronic conditions such as cardiovascular disease. As soon as a role for these molecules in the pathogenesis of such common diseases was established, novel therapeutic strategies were devised attempting to correct existing inflammatory mediator or cytokine imbalances, by either blocking the effects of certain cytokines or enhancing the presence of others. The first steps toward developing cytokine therapeutics were in the early 1980's. Since then there has been an explosion of interest in this area. The numerous animal and human cytokine based studies in the treatment of such disorders within the last twenty-five years are impossible to cover in a single journal issue. This issue therefore focuses on recent advances in this topic in 6 representative areas of research: chronic infections, allergy, asthma, cancer, transplant medicine and regenerative medicine. In the first article [1], Villar and Dongari-Bagtzoglou present recent information on advances in the use of cytokines as a therapeutic strategy in chronic bacterial, parasitic, fungal and viral infections. In all chronic infections it is generally accepted that for immune protection to take place, generation of a dominant Th1 or Th2 cell type cytokine response is required. In the first part of the article, the role of Th1, Th2 and proinflammatory cytokines as regulators of phagocytic cell function, cell-mediated immunity and humoral immunity, is described. Subsequently, the article discusses the regulation of host protective immunity by specific cytokines in some of the most common chronic infections and addresses potential therapeutic applications of such cytokines in animal models of infection and human trials when data are available. The paper by Woodfolk [2] addresses the role of cytokines in the pathogenesis of allergic disorders, such as asthma. Emerging concepts in the existing Th1/Th2 cytokine paradigm and the identification of a relevant molecular target for therapy are described. This article particularly highlights the challenges of dissecting the role of each cytokine as part of a complex network, in the development of allergic responses to antigens and the manifestation of allergic symptoms. The effects of existing and emerging therapies, which target Th1, Th2 and regulatory cytokines on established allergic responses are discussed. Camateros and coworkers [3] expand the information provided in this issue on allergic diseases by focusing on the role of Toll-like receptor (TLR)-regulated cytokines in the pathogenesis of asthma. In the introductory segment of this article TLR-mediated signaling is linked to specific immunomodulating cytokines, which contribute to the asthmatic phenotype. Specific therapeutic applications of TLR agonists and antagonists in animal models of the disease and future therapeutic prospects are extensively covered. In the fourth paper in this series Mutoh and coworkers [4] address the role of cyclooxygenase-derived mediators of inflammation (prostanoids) in the pathogenesis of cancer. Specific cellular mechanisms of disease pathogenesis, mediated by prostaglandins are addressed such as cell proliferation, modulation of apoptosis, angiogenesis and immune surveillance. Evidence in colon carcinogenesis for the contribution of cyclooxygenases in disease progression is presented. Furthermore, potential applications of prostanoid receptor inhibitors or agonists for cancer chemoprevention are discussed. In the article by De Sanctis et al. [5], cytokines and inflammatory mediators are discussed in the context of allotransplantation and allograft rejection. The specific cytokine-regulated immunologic mechanisms involved in acute and chronic graft rejection, are described.....