Submitted May 22, 2006
Accepted August 14, 2006
A role for IL-1 receptor antagonist or other cytokines in the acute therapeutic effects of IVIg?
Andrew R Crow, Seng Song, John W Semple, John Freedman, and Alan H Lazarus*
Canadian Blood Services, Department of Laboratory Medicine, St. Michael's Hospital
Department of Laboratory Medicine, St. Michael's Hospital
* Corresponding author; email: lazarusa{at}smh.toronto.on.ca.
The exact mechanism of action of IVIg in the amelioration of ITP is still unclear. Studies have suggested that IVIg may function through the regulation of cytokines, including Interleukin-1 receptor antagonist (IL-1Ra), an inhibitor of phagocytosis. Using a mouse model relevant to ITP, we confirm an increase in mouse serum levels of IL-1Ra after exposure to IVIg, yet a recombinant IL-1Ra did not ameliorate thrombocytopenia. IVIg has also been shown to affect the expression of other regulatory cytokines. We have also recently established that IVIg specifically targets activating Fc-
Rs on CD11c+ dendritic cells (DC) as its primary mechanism of action in the amelioration of murine ITP. Herein, we show that IVIg functions therapeutically in mice lacking specific cytokines or their receptors that can potentially affect DC/macrophage function (IL-1 Receptor, IL-4, IL-10, IL-12
, TNF-
, IFN- Receptor, MIP-1). This suggests that while IVIg may mediate the release of a variety of cytokines, the cytokines tested do not directly participate in the mechanism of IVIg action.
