Abstract
HIV establishes a chronic infection that is marked by the progressive depletion of CD4+ T-cells, yet the mechanisms by which this depletion arises are a matter of controversy. Evidence is accumulating that T CD4+ depletion is not effected solely by virus-mediated killing and that mechanisms involving T-cell dynamics play a major role in the pathogenesis of HIV infection. Hence antiretroviral therapy, by controlling viral replication alone, invariably fails to achieve the broadest immune reconstitution. This issue has strengthened the rationale to widely explore new adjuvant immunotherapy. Most work has been performed on IL-2, given its potential to correct HIVdriven immune defects, possibly translating in a more effective immune competency. Important insights stem from the IL-2-mediated immune reconstitution pattern, with a rise in peripheral turnover and thymopoiesis, IL-7 synthesis and functional markers, resulting in the correction of the skewed T-cell immunophenotype and cytokine milieu. Combined, these findings suggest that IL-2 has a beneficial effect in correcting the severe disruption in T-cell homeostasis induced by HIV, through the interaction with T-cells and cytokine microenvironment. However, whether or not these immunologic effects translate in an actual immunologic competency and therefore clinical benefit, still awaits demonstration from ongoing large, controlled clinical studies.
Keywords: Immune reconstitution, immunotherapy, interleukin-2
Current Molecular Pharmacology
Title: Immunological Mechanisms of Interleukin-2 (IL-2) Treatment in HIV/AIDS Disease
Volume: 2
Author(s): C. Tincati, A. d'Arminio Monforte and G. Marchetti
Affiliation:
Keywords: Immune reconstitution, immunotherapy, interleukin-2
Abstract: HIV establishes a chronic infection that is marked by the progressive depletion of CD4+ T-cells, yet the mechanisms by which this depletion arises are a matter of controversy. Evidence is accumulating that T CD4+ depletion is not effected solely by virus-mediated killing and that mechanisms involving T-cell dynamics play a major role in the pathogenesis of HIV infection. Hence antiretroviral therapy, by controlling viral replication alone, invariably fails to achieve the broadest immune reconstitution. This issue has strengthened the rationale to widely explore new adjuvant immunotherapy. Most work has been performed on IL-2, given its potential to correct HIVdriven immune defects, possibly translating in a more effective immune competency. Important insights stem from the IL-2-mediated immune reconstitution pattern, with a rise in peripheral turnover and thymopoiesis, IL-7 synthesis and functional markers, resulting in the correction of the skewed T-cell immunophenotype and cytokine milieu. Combined, these findings suggest that IL-2 has a beneficial effect in correcting the severe disruption in T-cell homeostasis induced by HIV, through the interaction with T-cells and cytokine microenvironment. However, whether or not these immunologic effects translate in an actual immunologic competency and therefore clinical benefit, still awaits demonstration from ongoing large, controlled clinical studies.
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Tincati C., Monforte d'Arminio A. and Marchetti G., Immunological Mechanisms of Interleukin-2 (IL-2) Treatment in HIV/AIDS Disease, Current Molecular Pharmacology 2009; 2 (1) . https://dx.doi.org/10.2174/1874467210902010040
DOI https://dx.doi.org/10.2174/1874467210902010040 |
Print ISSN 1874-4672 |
Publisher Name Bentham Science Publisher |
Online ISSN 1874-4702 |
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