title: Specific antibody in IV immunoglobulin for postsplenectomy sepsis.
abstract: OBJECTIVE
  Overwhelming postsplenectomy infection progresses rapidly and shows unacceptably high mortality even when treated with optimal antibiotics. Recent reports have described beneficial effects of intravenous immunoglobulin in sepsis. However, the underlying mechanisms, especially the roles of the pathogen-specific antibody fraction in intravenous immunoglobulin, remain unclear. We investigated the effects of intravenous immunoglobulin on overwhelming postsplenectomy infection and the role of pathogen-specific antibody.
  
  
  METHODS
  Prospective, controlled, and randomized animal study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Male C57BL/6JJcl mice.
  
  
  METHODS
  Mice underwent splenectomy or a sham operation at 8 weeks old. At 4 weeks after the operation, mice were injected intravenously with 106 colony-forming units pneumococcus. Intraperitoneal injection of 300 mg/kg IV immunoglobulins was conducted simultaneously with infection. Specific antibody-depleted IV immunoglobulin prepared using immunoprecipitation was also injected into the animals.
  
  
  RESULTS
  IV immunoglobulin markedly improved splenectomized mice survival. Removal of pneumococcus-specific antibody canceled it completely. Fluorescence microscopy results indicated significantly increased phagocytosis of antibody-bound bacteria in the livers of splenectomized mice treated with intact IV immunoglobulins. Immunomodulation, including suppression of marginal zone B-cell activation, was induced by IV immunoglobulin.
  
  
  CONCLUSIONS
  IV immunoglobulin showed a significantly protective effect on overwhelming postsplenectomy infection via enhancement of specific antibody-mediated phagocytosis in the liver. Specific antibody, more than immunological modulation, is crucial for effects of IV immunoglobulin on overwhelming postsplenectomy infection.
authors.affiliation: Department of Emergency and Critical Care Medicine, University Hospital, The University of Tokyo, Tokyo, Japan. Nakamurak-eme@h.u-tokyo.ac.jp
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kent
authors.initials: K
authors.lastname: Doi
authors.forename: Koji
authors.initials: K
authors.lastname: Okamoto
authors.forename: Syunnya
authors.initials: S
authors.lastname: Arai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueha
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakajima
authors.forename: Naoki
authors.initials: N
authors.lastname: Yahagi
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial; D001402:B-Lymphocytes / Q000166:cytology; D058491:Bacterial Load; D001769:Blood / Q000382:microbiology; D016207:Cytokines / Q000097:blood; D005434:Flow Cytometry; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D047468:Immunoprecipitation; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000187:drug effects; D011446:Prospective Studies; D011897:Random Allocation; D018805:Sepsis / Q000209:etiology / Q000628:therapy*; D013154:Spleen / Q000166:cytology / Q000382:microbiology; D013156:Splenectomy / Q000009:adverse effects*; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors