Picogram doses of lipopolysaccharide exacerbate antibody-mediated thrombocytopenia and reduce the therapeutic efficacy of intravenous immunoglobulin in mice.
Exacerbation of antibody-mediated thrombocytopenia following infection with viruses has recently been demonstrated in a mouse model of the disease. The phenomenon was caused by an increased activation of phagocytes through gamma-interferon secretion in response to infection. Endotoxins from Gram-negative bacteria are also known to be potent activators of phagocytic cells. The objective of the present work was to determine whether lipopolysaccharide (LPS) could exacerbate antibody-mediated thrombocytopenia in vivo and so alter the therapeutic efficacy of intravenous immunoglobulin (IVIg), using a mouse model of thrombocytopenia. Very low doses of LPS (picogram range) and of anti-platelet antibodies (nanogram range), which did not induce thrombocytopenia individually, could synergize in vivo, resulting in significant decreases in platelet counts. The therapeutic efficacy of IVIg in antibody-mediated thrombocytopenia was significantly reduced in presence of LPS. These in vivo observations further support a role for bacterial infections in the aetiology of immune thrombocytopenic purpura (ITP) and may contribute to better understand the recognized lack of efficacy of IVIg in a significant proportion of patients with ITP.
Tremblay
Tony
T
Department of Research and Development, Héma-Québec, QC, Canada.
Aubin
Eric
E
Lemieux
Réal
R
Bazin
Renée
R
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D005260:Female; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000382:microbiology; D013921:Thrombocytopenia / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D017211:Treatment Failure
D000906:Antibodies; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides