Absence of cytokine modulation following therapeutic infusion of intravenous immunoglobulin or anti‐red blood cell antibodies in a mouse model of immune thrombocytopenic purpura

Abstract

Human intravenous immunoglobulin (IVIg) and anti-D immunoglobulin preparations are used in the treatment of immune thrombocytopenic purpura (ITP). One mechanism proposed to explain their therapeutic effects in ITP patients is the induction of expression of anti-inflammatory cytokines, such as interleukin (IL)-10 or IL-1ra, leading to a reduction of phagocytic activity of the reticuloendothelial system. However, increased expression of pro-inflammatory cytokines was also noted following treatment of ITP patients, raising doubt on the actual contribution of anti-inflammatory cytokines in the therapeutic effects of IVIg and anti-D immunoglobulins. The present study evaluated the in vivo modulation of expression of a large array of inflammatory cytokines using a mouse model of thrombocytopenia. IVIg was not found to modulate cytokine expression although it efficiently prevented thrombocytopenia. In contrast, protective (M1/69) and non-protective (TER-119) anti-mouse red blood cell (RBC) antibodies (mimicking anti-D treatment) both increased the expression of CXCL-1 and CXCL-5. Thus, there was no relationship between inflammatory cytokine expression and prevention of thrombocytopenia by IVIg or anti-mouse RBC in the ITP mouse model. These results suggest that the increase in cytokine expression observed in ITP patients following IVIg or anti-D infusion is not required for their therapeutic effects but may rather represent a side-effect of the treatment.