Effects of Subcutaneous Interleukin‐2 Therapy on Phenotype and Function of Peripheral Blood Mononuclear Cells in Human Immunodeficiency Virus Infected Patients

Aladdin,; Larsen, Martin R.; Möller,; Ullum, Henrik; Buhl,; Gerstoft,; Pedersen, Bente Klarlund

doi:10.1046/j.1365-3083.2000.00673.x

Cited by 10 publications

(10 citation statements)

References 35 publications

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“…This finding is in accordance with those of several other studies [8,9,15]. However, we found that IL-2 treatment induced an impaired lymphocyte function expressed as a decreased proliferative response and decreased cytotoxic T cell (CTL) activity [16]. The purpose of this study was to investigate whether changed telomere lengths are associated with the previously observed depressed lymphocyte function.…”

Section: Introductionsupporting

confidence: 92%

“…There were no changes in antiretroviral regimens 3 months prior to initiation of IL-2 treatment or throughout the study. Blood samples were collected 4 weeks before therapy, at enrolment, and 4, 8,12,16,20,24,28,32 and 36 weeks after enrolment. The Danish National Health Board and the local ethics committee approved the trial, and all patients provided their written informed consent.…”

Section: Methodsmentioning

confidence: 99%

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Effects of Subcutaneous IL‐2 Therapy on Telomere Lengths in PBMC in HIV‐Infected Patients

Aladdin

Larsen

Schjerling³

et al. 2001

Scand J Immunol

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In this study we investigated the effect of interleukin-2 (IL-2) on mean terminal restriction fragment (TRF) lengths in peripheral blood mononuclear cells (PBMC). Ten human immunodeficiency virus (HIV)-infected individuals were included and IL-2 was administered subcutaneously with 3 Â 10 6 IU three times a week for 24 weeks. Mean TRF length was decreased on average by 267 bp at week 4 (P 0.03) and 286 bp at week 8 (P 0.09). Individual TRF changes at weeks 12, 16, 20 and 24 were highly variable. However, in the 12 weeks following therapy, TRF lengths generally increased reaching baseline levels by the end of the study. At baseline, mean TRF lengths were positively correlated to the ratio of naõ Ève and memory phenotype within both CD4 1 and CD8 1 cells. This study shows that IL-2 treatment induces transient shortened mean TRF lengths in PBMC from HIV-infected individuals, indicating that IL-2 enhances the lymphocyte count by peripheral proliferation or recruitment of memory T cells into the blood.

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Section: Introductionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Effects of Subcutaneous IL‐2 Therapy on Telomere Lengths in PBMC in HIV‐Infected Patients

Aladdin

Larsen

Schjerling³

et al. 2001

Scand J Immunol

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“…First, lymphocyte proliferative response, LAK and CTL functions are known to decrease following subcutaneous low-dose IL-2 administration to HIV-infected individuals and NK activity, following an initial increase, decreased below baseline levels during treatment of these patients. 30 Second, impaired NK cell activity might adversely impact on the control of minimal residual disease in cancer patients. Thus, an additional finding of this study was that NK activity was not significantly depressed after low-dose IL-2 treatment at any time point.…”

Section: Discussionmentioning

confidence: 99%

“…A similar reduction in CD45RA ϩ T cell count has already been reported at late time points after subcutaneous low-dose IL-2 administration. 30 This phenomenon has no apparent explanation and suggests that, similar to myelopoietic growth factors, IL-2 given soon after PBSCT also produces long-lasting immune effects with persistent modulation (observable until day 100 post-PBSCT) in the number of de novo generated T cells (ie naive CD45RA ϩ T cells). The detrimental effect of IL-2 addition on CD45RA ϩ T cell regeneration is surprising and confirms the lack of favorable post-PBSCT immune effects by IL-2.…”

Section: Discussionmentioning

confidence: 99%

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer

Perillo

Pierelli

Battaglia

et al. 2002

Bone Marrow Transplant

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Summary:This study evaluated the effects of low-dose IL-2 plus G-CSF/EPO on post-PBSC transplantation (PBSCT) immune-hematopoietic reconstitution and NK activity in patients with breast (BrCa) and ovarian cancer (OvCa). To this end, two consecutive series of patients were prospectively assigned to distinct post-PBSCT cytokine regimens (from day +1 to day +12) which consisted of G-CSF (5 g/kg/day) plus EPO (150 IU/kg/every other day) in 17 patients (13 BrCa and 4 OvCa) or G-CSF/EPO plus IL-2 (2 ؋ 10 5 IU/m 2 /day) in 15 patients (10 BrCa and 5 OvCa). Hematopoietic recovery and post-transplantation clinical courses were comparable in G-CSF/EPO-and in G-CSF/EPO plus IL-2-treated patients, without significant side-effects attributable to IL-2 administration. In the early and late post-transplant period a significantly higher PMN count was observed in G-CSF/EPO plus IL-2-treated patients (P ‫؍‬ 0.034 and P ‫؍‬ 0.040 on day +20 and +100, respectively). No significant differences were found between the two groups of patients in the kinetics of most lymphocyte subsets except naive CD45RA + T cells which had a delayed recovery in G-CSF/EPO plus IL-2 patients (P ‫؍‬ 0.021 on day +100). No significant difference was observed between NK activity in the two different groups, albeit a significantly higher NK count was observed in G-CSF/EPO plus IL-2 series on day +20 (P ‫؍‬ 0.020). These results demonstrate that low-dose IL-2 can be safely administered in combination with G-CSF/EPO early after PBSCT and that it exerts favorable effects on post-PBSCT myeloid reconstitution, but not on immune recovery.

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“…(15) Major players have emerged, and immunotherapy aimed at manipulating these has already shown promise. (22)(23)(24) The current challenge is to master the art of navigating the fine line between protection and pathology in TB. (25,26) …”

mentioning

confidence: 99%

Short Communication: Reduced Cytokine Secretions by LAK Cells of Pulmonary Tuberculosis Patients in Response to Tumor TargetsIn Vitro

Nirmala

Mathew

Narayanan

2002

Journal of Interferon & Cytokine Research

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Activation of macrophages and other immune components to release a series of proinflammatory cytokines is one of the first events in innate resistance to intracellular infections. Severe manifestations of tuberculosis (TB) could be caused by alterations in the balance of these cytokines. In this study, lymphokine-activated killer (LAK) cells of TB patients and normal individuals were generated by stimulation with cytokines in vitro. The LAK cells of both groups were further triggered with allogeneic tumor targets. Cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were estimated in the supernatants generated in the two groups. The aim was to see if infection with TB influenced the secretory capacity of the immune cells in vitro. Reduced cytokine profiles were observed in TB patients, indicating defective interactions between patient effector cells with allogeneic transformed cells compared with normal individuals. Partial restoration of IFN-gamma production was seen with a combination of cytokines interleukin-2 (IL-2) and IL-12 in TB patients. Based on the in vitro observations, we hypothesize that in vivo also there is diminished immune cell activation of effector cells in response to the presence of infected macrophages. This probably leads to a diminished secretory function that can be corrected by the use of such cytokines as IL-2 and IL-12. The effector populations of TB patients are probably in a state of target-induced anergy, allowing the bacteria to thrive, and immunomodulatory cytokines that improve the host immune response toward countering mycobacterial infection.

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Effects of Subcutaneous Interleukin‐2 Therapy on Phenotype and Function of Peripheral Blood Mononuclear Cells in Human Immunodeficiency Virus Infected Patients

Cited by 10 publications

References 35 publications

Effects of Subcutaneous IL‐2 Therapy on Telomere Lengths in PBMC in HIV‐Infected Patients

Effects of Subcutaneous IL‐2 Therapy on Telomere Lengths in PBMC in HIV‐Infected Patients

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer

Short Communication: Reduced Cytokine Secretions by LAK Cells of Pulmonary Tuberculosis Patients in Response to Tumor TargetsIn Vitro

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