Editorial [ Interleukin-10 Family - Old and New Promising Cytokines Guest Editors: Khusru Asadullah & Robert Sabat ]

Cytokines are key mediators of the immune system,playing a major role in health and disease. Their crucial importance in host defense, hematopoiesis, inflammation,autoimmunity, tumor and other diseases became obvious over the last two to three decades. Today, targeting components of the cytokine network represents a promising new therapeutic approach, which includes both strategies for antagonizing cytokine action as well the application of recombinant cytokines. Impressive examples are the antagonization of tumor necrosis factor (TNF)-alpha, which represents a breakthrough for the therapy of several inflammatory and autoimmune diseases, the interferon-alpha application, which improved therapy for several tumors, the interferon-beta therapy in patients with multiple sclerosis, the erythropoietin substitution in patients with kidney insufficiency, and the granulocyte-monocyte colony stimulating factor (GM-CSF) application in patients with immune deficiency [1-4]. Intervening into the cytokine network is already well established by using ‘biologicals’ i.e. recombinant proteins including cytokines, neutralizing anti-cytokines and antireceptor antibodies, soluble receptors and various fusion proteins. Novel small molecule approaches may either mimic the cytokine effects, inhibit the cytokine function, or modulate the cytokine expression, but are further down the road.Targeting of cytokines has contributed to the symptom-free life of thousands of patients and has even saved many lives to date. Currently, it is a billion dollar industry and this market will most likely continue to grow in the upcoming years. With the remarkable potential of cytokines in mind, it is no surprise that the discovery of novel cytokines significantly raises the interest of basic and applied research scientists in academia as well as in pharmaceutical companies. Their discoveries trigger questions particularly regarding their biological functions (such as whether they play an important role in disease) and their 'mode of action'. Many cytokines, discovered in the last few years, were delegated to the so-called IL-10 family [5]. Although IL-10 has beenknown since 1989, this family has only recently grown to be comprised of eight additional mediators, namely of IL-19, IL-20, IL-22, IL-24, IL-26, IL-28-alpha, IL-28-beta, and IL- 29 [6]. Interestingly, these cytokines were not grouped in a family based on similar biological effects but rather due to three other reasons: i) they show a similar amino acid sequence and secondary structure, ii) their genes have similar structures and are genomically clustered, and iii) these cytokines bind to receptor complexes composed of two different members of the cytokine receptor family class II. IL-10 is primarily an important immunosuppressive and anti-inflammatory cytokine in humans [7]. As far as the biological effects of the new members of the IL-10 family are known, these novel mediators do not appear to share IL-10's function. However, the current knowledge lets us assume that at least three of the new members also represent promising therapeutic targets. In fact, application of IL-24 is a possible new and potentially effective therapy for eliminating tumors [8]. Moreover, inhibition of the effects of IL- 20 and IL-22 may lead to the improvement of chronic skin diseases [9-11]. The possible therapeutic potential of influencing the effects of IL-20, IL-22, and IL-24 in addition to the contribution of expanding our knowledge on the immune system makes researching the biology of the IL-10 family members both very interesting and important.The purpose of this hot-topic issue is to review the current knowledge with regard to these important immune mediators and their receptors. Top experts contributed chapters for each of the IL-10 family members and their receptors.Thus, this hot-topic issue forms a comprehensive, state-ofthe-art volume giving a valuable overview. REFERENCES [1] Asadullah, K.; Sterry, W.; Trefzer, U. Exp. Dermatol. 2002, 11, 97- 106. [2] Disis, M.L. Oncology (Williston Park), 2005, 19, 5-9. [3] Henry, D.H.; Bowers, P.; Romano, M.T.; Provenzano, R. Arch Intern. Med., 2004, 164, 262-276. [4] Schottelius, A.J.; Moldawer, L.L.; Dinarello, C.A.; Asadullah, K.;Sterry, W.; Edwards, C.K., 3rd. Exp. Dermatol., 2004, 13, 193-222. [5] Volk, H.; Asadullah, K.; Gallagher, G.; Sabat, R.; Grutz, G. Trends Immunol., 2001, 22, 414-417. [6] Pestka, S.; Krause, C.D.; Sarkar, D.; Walter, M.R.; Shi, Y.; Fisher, P.B. Annu Rev. Immunol., 2004, 22, 929-979. [7] Moore, K.W.; de Waal Malefyt, R.; Coffman, R.L.; O'Garra, A.Annu. Rev. Immunol., 2001, 19, 683-765. [8] Sauane, M.; Gopalkrishnan, R.V.; Sarkar, D.; Su, Z.Z.; Lebedeva,I.V.; Dent, P.; Pestka, S.; Fisher, P.B. Cytokine Growth Factor Rev., 2003, 14, 35-51......