Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.

Abstract

HIV infection is characterized by the reduction of the CD4 ϩ , CD45RA ϩ , CD26 ϩ , and CD28 ϩ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-␥ ; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4 ϩ , CD45RA ϩ , CD45R0 ϩ , and CD26 ϩ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-␥ , RANTES, and sCD30 in HIV ϩ patients.10 HIV ϩ patients with CD4 cell counts between 200 and 500 cells/mm 3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4 ϩ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA ϩ /CD26 ϩ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-␥ , and sCD30 were significantly upregulated.These results demonstrate that rIL-2 in HIV ϩ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-␥ . These effects may be beneficial to HIV ϩ patients by improving their immune response to microorganisms or vaccines. ( J. Clin.

IL-2–induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation

“…1,13,14 The same observation was made in this study. In the IL-2 group the median percent of CD4 ϩ T cells expressing CD25 increased from 19.6% to 53% and the CD4 ϩ /CD25 ϩ T-cell count increased from 89 cells/L to 360 cells/L (P Ͻ .001).…”

Exogenous Interleukin-2 Administration Corrects the Cell Cycle Perturbation of Lymphocytes from Human Immunodeficiency Virus-Infected Individuals

“…Interestingly, a recent report by Kovacs and colleagues indicates that IL-2 therapy also induces an increased expression of its receptor, CD25, on CD4 ϩ T cells (32a), perhaps suggesting a role for exogenous IL-2 in increasing the T-cell responsiveness to suboptimal levels of endogenous cytokine. However, in the clinical setting it is difficult to assess if there is an additional in vivo antiapoptotic effect of IL-2 as opposed to highly active antiretroviral therapy (HAART) alone (2,5,13,46), given the fact that HAART itself induces a striking reduction of the HIV-induced hyperimmune activation and apoptosis (4,7,29). It is therefore still difficult, at this time, to determine to what extent the intrinsic defect of the endogenous IL-2 autocrine and paracrine function is directly responsible in vivo for the observed cell cycle perturbation.…”

Lowered Serum Dipeptidyl Peptidase IV Activity is Associated with Depressive Symptoms and Cytokine Production in Cancer Patients Receiving Interleukin-2-Based Immunotherapy

“…In HIV ϩ patients, IL-2 immunochemotherapy results in a significant increase in the number of CD26 ϩ T cells (De Paoli et al 1997). On human natural killer cells, CD26 expression is inducible by IL-2 (Yamabe et al 1997).…”