Current perspectives on cytokines for anti-retroviral therapy in AIDS related B-cell lymphomas.
The development of high-grade B-cell lymphoma in Acquired Immunodeficiency Syndrome (AIDS) patients is a relatively late manifestation induced by Human Immunodeficiency Virus-1 (HIV) infection and is considered to be an AIDS-defining condition. Multiple, ongoing molecular and cytogenetic aberrations appear necessary for the development of AIDS-related lymphoma. Studying a panel of human B-cell lines derived from patients with Burkitt's lymphoma (BL) and AIDS-associated Burkitt's lymphoma (AIDS-BL) we had described constitutive expression and secretion of large amounts of Interleukin-16 (IL-16), Macrophage Inflammatory Protein-1alpha (MIP-1alpha), Macrophage Inflammatory Protein-1beta (MIP-1beta), Interleukin-12 (IL-12), Interleukin-10 (IL-10), and Interleukin-7 (IL-7). Some of these cytokines like IL-16, MIP-1beta, MIP-1alpha and Regulated upon activation normal T expressed and secreted (RANTES) are shown to have inhibitory effect on HIV replication. Interestingly, we identified a novel transcription factor family, Macrophage Inflammatory Protein-1alpha Nuclear Protein (MNP), which is suggested as a potential target for anti-retroviral therapy based on the implication of its role and involvement as a key regulator of MIP-1alpha. It is apparent, that HIV induces the production of a cascade of cytokines and cytokine receptors. Some of these molecules serve to increase the infection and replication of HIV per se, and some others serve to induce a state of B-cell growth, activation, and differentiation. This review attempts to delineate the complex mechanisms of viral, B-cell, oncogene, cytokine/cytokine receptor and transcription factor interactions that are involved in AIDS associated lymphomagenesis. Unfolding the relationship between cytokines and the underlying mechanisms of the disease will not only help in understanding the pathophysiology but also will facilitate focusing on the development of new diagnostic and therapeutic strategies.
Sharma
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Laboratory of Cytokine Research, Department of Biology, 11000 University Parkway, University of West Florida, Pensacola, Florida 32514-5751, USA. vsharma@uwf.edu
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D018121:Receptors, Cytokine; D014157:Transcription Factors