title: The role of cytokines in the pathogenesis and management of AIDS-related lymphomas.
abstract: AIDS-related non-Hodgkin lymphomas (AIDS-NHL) consistently derive from B-cells and are characterized by extreme clinical aggressiveness. At histological level, AIDS-NHL are classified as AIDS-related Burkitt's lymphoma (AIDS-BL), AIDS-related diffuse large cell lymphoma (AIDS-DLCL) and AIDS-related primary effusion lymphoma (AIDS-PEL). The role of cytokines in the pathogenesis and management of AIDS-NHL has been studied to a certain extent. Production of large quantities of human IL-10 occurs frequently in AIDS-BL and correlates with latent EBV infection of the tumor clone. Lesser amounts of the cytokine are released in EBV negative cases. The pathogenetic role of IL-10 in AIDS-BL is suggested by the observation that IL-10 antisense oligonucleotides inhibit proliferation of the lymphoma. A significant fraction of AIDS-BL cell lines produce TNFbeta. Among AIDS-NHL, the release of TNFbeta appears to be specific for AIDS-BL. The pathogenetic relevance of TNFbeta in lymphomagenesis is suggested by the observation that some BL cell lines use TNFbeta as an autocrine growth factor. Some cases of AIDS-BL, particularly those carrying EBV infection, also secrete IL-6, IL-7 and IL-12. With respect to AIDS-DLCL, many cases express the IL-6R, rendering these cells responsive to the paracrine stimulation by the IL-6 produced by nearby T-cells, macrophages and endothelial cells which are frequently abundant in these tumor samples. The tumor clone itself, however, generally fails to release IL-6. AIDS-PEL is characterized by secretion of large amounts of IL-6 and IL-10. Some PEL cases also release oncostatin M. Apart from human IL-6, PEL also express viral IL-6, which is encoded by the HHV-8 genome. The biological relevance of both IL-6 and IL-10 in PEL proliferation and growth has been recently clarified in vitro and in vivo. Overall, these data suggest that activation of different cytokine loops clusters with different clinico-pathologic categories of AIDS-NHL and may represent the potential target of novel therapeutic strategies.
authors.affiliation: Department of Medical Sciences, Amedec Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Fassone
authors.forename: G
authors.initials: G
authors.lastname: Gaidano
authors.forename: C
authors.initials: C
authors.lastname: Ariatti
authors.forename: D
authors.initials: D
authors.lastname: Vivenza
authors.forename: D
authors.initials: D
authors.lastname: Capello
authors.forename: A
authors.initials: A
authors.lastname: Gloghini
authors.forename: A M
authors.initials: AM
authors.lastname: Cilia
authors.forename: D
authors.initials: D
authors.lastname: Buonaiuto
authors.forename: D
authors.initials: D
authors.lastname: Rossi
authors.forename: C
authors.initials: C
authors.lastname: Pastore
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: G
authors.initials: G
authors.lastname: Saglio
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000209:etiology* / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines