REVIEW Vijay P. Khatri ? Michael A. Caligiuri A review of the association between interleukin-10 and human B-cell malignancies Received: 11 February 1998 / Accepted: 26 February 1998 Key wordsmInterleukin-10 ? Lymphoma ? Epstein-Barr virus ? B lymphocyte ? Lymphoproliferative disorders Introduction Several studies have provided evidence for the role of human interleukin-10 (IL-10) in the pathogenesis of malig- nant B cell lymphoproliferation and lymphomas. Produc- tion of IL-10 may confer a selective advantage upon B cell malignancies by directly enhancing the survival and pro- liferation of tumor cells and by impairing host immune responses via its suppressive effects on macrophages and T cells. This review will outline the biological activity of IL-10, the relationship with Epstein-Barr Virus (EBV), and the experimental and clinical data that evaluate its associa- tion with B cell malignancies. Biology of IL-10 IL-10 is a pleiotropic cytokine that was initially known as the cytokine-synthesis-inhibiting factor, and its discovery was based upon characterization of its biological activity [13]. It is a 18-kDa acid-sensitive protein comprised of 160 amino acids. Unlike murine (mu) IL-10, which is glycosy- lated at the N terminus, human (hu) IL-10 lacks detectable carbohydrate moieties [40]. This glycosylation, however, is not necessary for its biological activity. In its active form, huIL-10 exists as a 37-kDa non-covalently bound dimer. The gene for IL-10 is present as a single copy in the genome and has been localized to chromosome 1 in the mouse and in humans [19]. Interestingly, both species of IL-10 exhibit a strong DNA and amino acid sequence homology to the open reading frame in the EBV genome called BCRF-1 [26]. Since huIL-10 and BCRF-1 [viral (v) IL-10] are closely related in amino acid sequence, it is postulated that EBV may have captured this mammalian gene during evolution to confer a survival advantage [27]. vIL-10 is a 17-kDa non-glycosylated polypeptide, which shares most of the functional activities with huIL-10, including receptor binding [15]. However, the specific activity of vIL-10 is three- to tenfold lower than that of huIL-10. Production of IL-10 IL-10 is produced by monocytes, macrophages, B cells and activated T cells [16]. CD4 + T cells can be separated into subsets based on a particular profile of their cytokine production following stimulation. The cytokines, in turn, dictate which response (humoral or cellular) the T cells will promote. The cell-mediated response has been referred to as the type 1 response, and the CD4 T cells that promote the type 1 response are called Th1 cells [30]. The prototypic type 1 or th1 cytokines are IL-2 and interferon g (IFNg). The humorally mediated response is called the type 2 response and the CD4 + T cells that promote the type 2 response are called Th2 cells. The prototypic type 2 or Th2 cytokines are IL-4, IL-5, IL-6, IL-10 and IL-13 [31]. In humans, though Th2 clones are the main source of IL-10, many Thl clones will also secrete IL-10 following antigen- specific stimulation [48]. CD45RO + (memory) T cells produce tenfold higher amounts of IL-10 than do This work was supported by grants (CA09581 and CA65670) from the National Institute of Health V.P. Khatri Division of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York, NY 14263, USA M.A. Caligiuri Divisions of Hematology/Oncology and Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, OH 4321, USA M.A. Caligiuri ( ) 458A Starling-Loving Hall, 320 West 10th Avenue, Columbus, Ohio OH 43210, USA Tel.: +1 ± 614 ± 293 ± 7521; Fax: +1 ± 614 ± 293 ± 7522 e-mail: caligiuri-l@medctr.osu.edu Cancer Immunol Immunother (1998) 46: 239 ± 244 Ó Springer-Verlag 1998