Controlled Trial of Interleukin-2 Infusions in Patients Infected with the Human Immunodeficiency Virus

Kovacs, Joseph A.; Vogel, Susan; Albert, Jeffrey M.; Falloon, Judith; Davey, Richard T.; Walker, Robert; Polis, Michael A.; Spooner, Katherine; Metcalf, Julia A.; Baseler, Michael; Fyfe, Gwen; Lane, H. Clifford; Dewar, Robin; Masur, Henry

doi:10.1056/nejm199610313351803

Cited by 390 publications

(221 citation statements)

References 22 publications

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“…To our knowledge, no other study has reported such associations between (27). The role of IL-2 in the stimulation of proliferation and differentiation of CD4 and CD8 T lymphocytes is well known, and consistent with these results (28)(29)(30). These findings indicate that khat has indeed the potential to significantly alter the immune response.…”

Section: Discussionsupporting

confidence: 80%

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Abuye

Tsegaye²,

West

et al. 2005

J Clin Immunol

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To study the determinants of CD4% and CD4 counts among HIVnegative Ethiopians, and to identify factors susceptible to explain the low CD4 counts observed among Ethiopian subjects. Cohort studies among factory workers in Akaki and Wonji, Ethiopia. Clinical and laboratory examinations, including determination of HIV serological status and T-cell subsets, were performed during follow-up visits every six months. In addition, micronutrients (retinol, carotenoids, tocopherol, transferrin receptor, and selenium) plasma concentrations were determined in a subset of 38 HIV-positive and 121 HIV-negative participants. HIV-negative participants with at least one CD4 count measurement were 157 females in Akaki, 203 males in Akaki, and 712 males in Wonji. CD4 counts were independently and positively associated with body mass index (through an increase in lymphocyte counts), female gender (through an increase in CD4%), cigarette smoking (through an increase in CD4%), khat chewing (through an increase in both lymphocyte counts and CD4%), and Akaki study site (through a large increase in lymphocyte counts compensating a decrease in CD4%). Intestinal parasitic infections were not associated with CD4% or CD4 counts. Retinol, carotenoids, and α-tocopherol plasma concentrations decreased with HIV infection and advancing immunosuppression, but were not associated with CD4 counts among HIV-negative subjects. Low body mass index among Ethiopians may have contributed to their overall low CD4 counts. Other factors remain to be elucidated.

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Section: Discussionsupporting

confidence: 80%

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Abuye

Tsegaye²,

West

et al. 2005

J Clin Immunol

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“…Thence, innovative approaches aimed at improving immune reconstitution have been proposed as a complement to ART. In particular, cytokines that play an essential role in T cell homeostasis and proliferation, such as IL-2 and IL-7, currently are under clinical investigation (18). In this study, we demonstrated that IL-7 exerts protective effects against the spontaneous apoptosis of both CD4 ϩ and CD8 ϩ T cells derived from HIV-1-infected individuals.…”

Section: Discussionmentioning

confidence: 60%

“…For example, interleukin 2 (IL-2), a cytokine that induces a marked increase in the number of total and naïve CD4 ϩ T cells in HIV-1-infected patients (18), was shown to reduce the levels of T cell apoptosis both in vivo (19) and ex vivo (20); the long-term benefits of this therapeutic regimen are being determined in clinical trials. Another cytokine that is under evaluation as a potential agent of immune reconstitution in HIV-1 infection is IL-7, a key factor in the generation, activation, and homeostasis of the T cell compartment of the immune system (21).…”

mentioning

confidence: 99%

Interleukin 7 reduces the levels of spontaneous apoptosis in CD4⁺and CD8⁺T cells from HIV-1-infected individuals

Vassena

Proschan

Fauci

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Apoptosis has been suggested as one of the major mechanisms of CD4 ؉ T cell depletion during the course of HIV type 1 (HIV-1) infection. Here, we show that interleukin 7 (IL-7), a nonredundant cytokine that plays essential roles in the generation and homeostasis of the T cell compartment of the immune system, exerts strong antiapoptotic effects ex vivo on both CD4 ؉ and CD8 ؉ T cells derived from HIV-1-infected subjects. The level of IL-7-mediated reduction of apoptosis was inversely correlated with the number of circulating CD4 ؉ T cells, indicating a higher sensitivity to IL-7 effects in patients with more advanced disease. The antiapoptotic effect of IL-7 was uncoupled from the induction of cellular proliferation or endogenous HIV-1 replication. These results provide a further rationale for consideration of IL-7 as an agent of immune reconstitution in HIV-1 infection.T lymphocytes ͉ immunodeficiency ͉ immune reconstitution ͉ programmed cell death ͉ cytokines

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“…In its capacity as a potent immunostimulator, IL-2 has also been explored as an ameliorative treatment for T-cell loss as a consequence of HIV infection (Lotze et al 1984;Kovacs et al 1996). In spite of early promise, a recently reported longterm study suggests no real improvement in disease progression, immune function, or eventual outcome (Abrams et al 2009).…”

Section: Il-2 Agonists: Oncology and Infectious Diseasementioning

confidence: 99%

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

Wilson

Arkin

2010

Current Topics in Microbiology and Immunology

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Controlled Trial of Interleukin-2 Infusions in Patients Infected with the Human Immunodeficiency Virus

Abstract: In patients with HIV infection and base-line CD4 counts above 200 cells per cubic millimeter, intermittent infusions of interleukin-2 produced substantial and sustained increases in CD4 counts with no associated increase in plasma HIV RNA levels.

Cited by 390 publications

References 22 publications

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Interleukin 7 reduces the levels of spontaneous apoptosis in CD4⁺and CD8⁺T cells from HIV-1-infected individuals

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

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Controlled Trial of Interleukin-2 Infusions in Patients Infected with the Human Immunodeficiency Virus

Abstract: In patients with HIV infection and base-line CD4 counts above 200 cells per cubic millimeter, intermittent infusions of interleukin-2 produced substantial and sustained increases in CD4 counts with no associated increase in plasma HIV RNA levels.

Cited by 390 publications

References 22 publications

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Determinants of CD4 Counts Among HIV-Negative Ethiopians: Role of Body Mass Index, Gender, Cigarette Smoking, Khat (Catha Edulis) Chewing, and Possibly Altitude?

Interleukin 7 reduces the levels of spontaneous apoptosis in CD4+and CD8+T cells from HIV-1-infected individuals

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

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Interleukin 7 reduces the levels of spontaneous apoptosis in CD4⁺and CD8⁺T cells from HIV-1-infected individuals