Immunologic reconstitution by interleukin-2: facts and open questions

Interleukin-2 (IL-2), one of the most potent immunoregulatory and inflammat ory cytokines, is being tested in phase III clinical trials in order to dem onstrate its efficacy in combination with current antiviral agents in preve nting the occurrence of opportunistic infections and death in individuals i nfected by the human immunodeficiency virus (HIV). In the meantime, its cap acity to boost the number of CD4+ T cells in peripheral blood has been conf irmed by a number of individual phase I/II trials conducted in different co untries by independent investigators. In the face of this remarkable result , little is known of the effects exerted by this cytokine once administered to infected individuals in terms of its impact on different immunologic fu nctions. The recent acquisitions on the important role played by latently i nfected cells in in vivo infection in reinitiating HIV replication and cyto pathicity once antiviral therapy is suspended or becomes suboptimal, has sh ed new light on the possibility of utilizing immunologic strategies, includ ing IL-2, for eradicating the virus from latent reservoirs. Results from a clinical trial conducted at our Institute indicate a decrease in lymphocyte -associated HIV DNA after IL-2 administration, supporting this hypothesis.