title: 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.
authors.affiliation: Department of Research and Development, Héma-Québec, QC, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Aubin
authors.forename: Réal
authors.initials: R
authors.lastname: Lemieux
authors.forename: Renée
authors.initials: R
authors.lastname: Bazin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000276:immunology; D011696:Purpura, Thrombocytopenic / Q000276:immunology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology
chemical_list: D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies