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.
AuthorsTony Tremblay, Eric Aubin, Réal Lemieux, Renée Bazin
JournalBritish journal of haematology (Br J Haematol) Vol. 139 Issue 2 Pg. 297-302 (Oct 2007) ISSN: 0007-1048 [Print] England
PMID17897306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies
  • Immunoglobulins, Intravenous
  • Lipopolysaccharides
  • Animals
  • Antibodies (immunology)
  • Female
  • Immunoglobulins, Intravenous
  • Lipopolysaccharides (pharmacology)
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Purpura, Thrombocytopenic, Idiopathic (immunology, microbiology)
  • Thrombocytopenia (immunology, microbiology, therapy)
  • Treatment Failure

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