The role of cytokines in the pathogenesis and management of AIDS-related lymphomas

AIDS-related non-Hodgkin lymphomas (AIDS-NHL) consistently derive from B-ce lls and are characterized by extreme clinical aggressiveness. At histologic al 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 pathogen esis and management of AIDS-NHL has been studied to a certain extent. Produ ction of large quantities of human IL-10 occurs frequently in AIDS-BL and c orrelates with latent EBV infection of the tumor clone. Lesser amounts of t he 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 oligonu cleotides inhibit proliferation of the lymphoma A significan fraction of AIDS-BL cell lines produce TNF beta. Among AIDS-NH L, the release of TNF beta appears to be specific for AIDS-BL. The pathogen etic relevance of TNF beta in lymphomagenesis is suggested by the observati on that some BL cell lines use TNF beta as an autocrine growth fat:tor. Som e 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 ce lls 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 r elease 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 b iological relevance of both IL-6 and IL-10 in PEL proliferation and growth has been recently clarified in vitro anti in vivo. Overall, these data sugg est that activation of different cytokine loops clusters with different cli nico-pathologic categories of AIDS-NHL and may represent the potential targ et of novel therapeutic strategies.