Editorial [Hot Topic: Recent Progresses in "Atypical" Applications of Cytokine and Anti-Cytokine (Executive Editor: Atsushi Oda)]

Recently several issues of Current Pharmaceutical Design have been dedicated to cytokines and their clinical applications. The topics on conventional and novel aspects in the field have been extensively covered by the reviews in them. As such, my purpose is to bring up-to-date information on somewhat "atypical" cytokine-related therapies. In this issue of Current Pharmaceutical Design, I invited six experts and their associates to present comprehensive reviews on these emerging topics. I would like to briefly introduce these exciting reviews. Feller and Lewitzky summarize the biology of adapter proteins, with emphasis on Crk and grb2. Both Crk and grb2 are classical adapters of protein-to-protein interaction without known catalytic domains. Alongwith other adapters, CrkL (Crk-like) and Nck, they are involved in signaling, triggered by ligasion of numerous cytokine/growth factor receptors. With 384 references, the readers will find this review exceptionally useful, to keep up with the rapid progresses in our understanding of these adapters and their ligands. Moreover, they also present the potential development of pharmacological reagents, which may modify the protein-to-protein interactions. It is seemingly a challenge, given that these adapters are keys players in so many different signaling pathways. On the other hand, once developed, such reagents may have very widespread applications in diverse clinical settings. Next, Ariga summarizes the development of gene therapy for treatment of primary immunodeficiency [2]. Recombinant cytokines are quite expensive and have only short half life time. Obviously, a gene therapy may be a choice for continual administration of cytokines. Among numerous trials of the gene therapies, those for treatment of immunodeficiency have been most successful. However, as he presents, there appears to be serious inherent problems in the therapy. Recombinant G-CSF has been extensively used to facilitate recovery of peripheral neutrophil counts following chemotherapy and/or bone marrow transplantation. It is also used for mobilization of multipotent immature hematopoietic cells for transplantation. Somewhat atypical, but the most promising utilization of the cytokine is for the treatment of ischemic heart diseases. This review by Komuro's group [3] is a sequel to a review, recently published in Current Pharmaceutical Design [4]. The readers may notice numerous and sometimes-conflicting evidences presented in the fields. Their well-balanced review gives pretty nice pictures of somewhat chaotic situations. Protection of cells from apoptosis is mediated by cytokines. Surprisingly, cilostazol, a well-established, anti-platelet reagent [5], may have a "cytokine-like" function and rescue neuronal cells in ischemic regions. This interesting application of cilostazol is reviewed by Hong's group, who has actually published most of works on this unique aspect of the anti-platelet reagent [6]. Finally, I have also asked two expert groups to summarize two naturally occurring cytokine-like substances. Yatomi, who has established that platelets are a major source of circulating sphingosine 1-phophate, concisely summarizing the diverse functions of the bioactive-lipid [7]. Agonists and antagonists of its receptors are being developed and potential application of these in clinical setting is also described in depth. Kuroki's group calls attention to novel and evolving fields of lung surfactant proteins [8]. The cytokine-like function of these proteins, which regulates the innate immunity, is well presented. They are not just surfactants, but actually are key players in inflammation and immunity in lung tissues. I hope that the readers will really enjoy these reviews on the emerging field of cytokine and anti-cytokine therapies, just as I do. References [1] Feller SM, Lewitzky M. Potential disease targets for drugs that disrupt protein-protein interactions of Grb2 and Crk family adaptors. Curr Pharm Design 2006; 12(5): 529-548. [2] Ariga T. Gene therapy for primary immunodeficiency diseases; recent progress and misgivings. Curr Pharm Design 2006; 12(5): 549-556. [3] Tateno K, Minamino T, Miyauchi H, Kunieda T, Komuro I. Application of Hematopoietis Cells to Therapeutic......