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J Immunol. 2008 Jan 1;180(1):44-8.

Cutting edge: mechanism of enhancement of in vivo cytokine effects by anti-cytokine monoclonal antibodies.

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1
Immunobiology Graduate Program, University of Cincinnati College of Medicine, and Division of Immunobiology, Children's Hospital Medical Research Foundation, Cincinnati, OH 45267, USA.

Abstract

Inhibitory anti-cytokine mAbs are used to treat cytokine-mediated disorders. Recently, however, S4B6, an anti-IL-2 mAb that blocks IL-2 binding to IL-2Ralpha, a receptor component that enhances affinity but is not required for signaling, was shown to enhance IL-2 agonist effects in vivo. We evaluated how S4B6 enhances IL-2 effects and whether a similar mechanism allows mAbs to IL-4 to enhance IL-4 effects. Induction of T cell proliferation by IL-2/S4B6 complexes did not require complex dissociation and was IL-2Ralpha independent. S4B6 increased IL-2 agonist effects by increasing in vivo half-life, not by focusing IL-2 onto cells through Fc receptors. In contrast to IL-2/S4B6 complexes, anti-IL-4 mAb enhancement of in vivo IL-4 effects required IL-4/anti-IL-4 mAb complex dissociation. Thus, agonist effects observed with high doses of anti-IL-2 mAb are most likely only applicable for mAbs that maintain cytokine half-life without blocking binding to receptor signaling components.

PMID:
18097002
[Indexed for MEDLINE]
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