Pharmacokinetic Alteration in Rats of Recombinant Interleukin-2 (rIL-2) by Immunocomplexing with a Monoclonal Antibody against rIL-2.

Sato, Jun; Hamaguchi, Naoru; Doken, Kazuhiro; Iwasa, Satoru; Ogawa, Yasuaki; Toguchi, Hajime

doi:10.1248/bpb.17.535

Cited by 6 publications

(2 citation statements)

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“…Alternatively, cytokines in complex with anti-cytokine Abs can prolong the half-life and activity of cytokines (61–66). Supporting this, hypersensitivity can be suppressed by IL-2 in complex with IgG2b with increased stability and half-life (67).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells

Wilson

Pesce

Ramalingam

et al. 2008

The Journal of Immunology

104

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*Regulatory T cells (Treg) play a decisive role in many diseases including asthma and allergen-induced lung inflammation. However, little progress has been made developing new therapeutic strategies for pulmonary disorders. In the current study we demonstrate that cytokine:antibody complexes of IL-2 and anti-IL-2 mAb reduce the severity of allergen-induced inflammation in the lung by expanding Tregs in vivo. Unlike rIL-2 or anti-IL-2 mAb treatment alone, IL-2:anti-IL-2 complexes dampened airway inflammation and eosinophilia while suppressing IL-5 and eotaxin-1 production. Mucus production, airway hyperresponsiveness to methacholine, and parenchymal tissue inflammation were also dramatically reduced following IL-2:anti-IL-2 treatment. The suppression in allergic airway disease was associated with a marked expansion of Tregs (IL-10 ؉ CD4 ؉ CD25 ؉ and Foxp3 ؉ CD4 ؉ CD25 ؉ ) in the tissues, with a corresponding decrease in effector T cell responses. The ability of IL-2:anti-IL-2 complexes to suppress airway inflammation was dependent on Treg-derived IL-10, as IL-10 ؉/؉ , but not IL-10 ؊/؊ Tregs, were capable of mediating the suppression. Furthermore, a therapeutic protocol using a model of established airway allergy highlighted the ability of IL-2:anti-IL-2 complexes to expand Tregs and prevent successive airway inflammation and airway hyperresponsiveness. This study suggests that endogenous Treg therapy may be a useful tool to combat the rising incidence of allergic airway disease.

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Section: Discussionmentioning

confidence: 99%

Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells

Wilson

Pesce

Ramalingam

et al. 2008

The Journal of Immunology

104

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“…Increases in the stability of complexed IL-2, IL-3, IL-4, IFN-␣, and IL-6 (13)(14)(15)(16)(17)(18)(19)(20)(21) and in the biological activity of the cytokine complex for IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, IFN-␥, and TNF (2, 5, 16 -29) have been demonstrated. In addition to these complexes formed with Ab, recent studies established the increase of biological activity of IL-15 complexed with the IL-15 receptor chain ␣ (30,31).…”

mentioning

confidence: 99%

IL-2/Anti-IL-2 Antibody Complex Enhances Vaccine-Mediated Antigen-Specific CD8+ T Cell Responses and Increases the Ratio of Effector/Memory CD8+ T Cells to Regulatory T Cells

Mostböck

Lutsiak

Milenic

et al. 2008

The Journal of Immunology

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IL-2 is well described as a cytokine with two markedly distinct functionalities: as a necessary signal during CD4+ and CD8+ T cell activation/expansion and as an essential cytokine for the maintenance of CD4+CD25+FoxP3+ T cells (regulatory T (TREG) cells) during homeostasis. In this study we demonstrate for the first time that, compared with the use of IL-2 alone, a complex of IL-2 and anti-IL-2 Ab (IL-2 complex) enhances the effectiveness of a viral vaccine in a mouse model with known Ag specificity. IL-2 complex led to an increase in the number of Ag-specific effector/memory CD8+ T cells, cytokine production, and CTL lysis following Ag-specific restimulation in a vaccination setting. Our results further demonstrate that this effect is temporary and declines over the course of a few days after the IL-2 complex treatment cycle. Moreover, in contrast to the use of IL-2 alone, IL-2 complex greatly increased the ratio of effector/memory CD8+ T cells to TREG cells. This phenomenon can thus potentially be used in the enhancement of immune responses to vaccination.

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Treatment-induced antibodies to interleukin-2

Prümmer¹

1997

Antibodies in Cytokines

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Pharmacokinetic Alteration in Rats of Recombinant Interleukin-2 (rIL-2) by Immunocomplexing with a Monoclonal Antibody against rIL-2.

Cited by 6 publications

References 0 publications

Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells

Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells

IL-2/Anti-IL-2 Antibody Complex Enhances Vaccine-Mediated Antigen-Specific CD8+ T Cell Responses and Increases the Ratio of Effector/Memory CD8+ T Cells to Regulatory T Cells

Treatment-induced antibodies to interleukin-2

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