title: IL-10 plasma levels are elevated after LPS injection in splenectomized A/J mice.
abstract: BACKGROUND
  Splenectomy is clinically indicated in certain cases of hypersplenism and splenic trauma. However, it is associated with serious complications, in particular, reduced clearance of encapsulated organisms and a high incidence of sepsis, which has been coined overwhelming post-splenectomy sepsis (OPSS). In addition to the role of the spleen in the clearance of microorganisms, this organ may be involved in regulation of the inflammatory response. We investigated the effect of splenectomy on the inflammatory process induced by LPS in a murine model that resembles, in part, the pathophysiological aspects of sepsis.
  
  
  METHODS
  Male mice (8-weeks-old) from different inbred strains were randomized into three groups: splenectomized (SPX), sham operated (SHAM), and non-operated controls (NoOp). After 9 days of recovery, mice were injected with LPS (15 mg/kg) and cytokine plasma levels were measured by ELISA at 1.5 or 6 h after injection. Peritoneal macrophages (PMphi) were isolated from the three groups, and cytokine production was evaluated after incubation with LPS in culture conditions.
  
  
  RESULTS
  IL-10 plasma levels were elevated in SPX A/J mice (6.7 +/- 0.4 mug/ml) after injection of LPS (15 mg/kg) compared to NoOp A/J mice (4.2 +/- 0.2 mug/ml, P < 0.05). Similar elevation in IL-10 plasma levels was detected in SPX DBA/2J mice as compared to NoOp DBA/2J mice, but not in C57BL/6J and BALB/cJ mice. In contrast, SPX AKR mice displayed lower IL-10 levels than NoOp mice. PMphis from SPX A/J mice produced elevated levels of IL-10 compared to PMphis from SHAM or NoOp A/J mice, mimicking the in vivo observations.
  
  
  CONCLUSIONS
  Our data suggest that the spleen plays an important role in modulating the inflammatory process induced by LPS, extending beyond passive clearance of encapsulated organisms. In addition, the contribution of the spleen to the inflammatory process may be influenced by the genetic background.
authors.affiliation: Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Torres
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Vega
authors.forename: Mazen
authors.initials: M
authors.lastname: Bedri
authors.forename: Daniel
authors.initials: D
authors.lastname: Saad
authors.forename: Heiko
authors.initials: H
authors.lastname: Trentzsch
authors.forename: Roger H
authors.initials: RH
authors.lastname: Reeves
authors.forename: Antonio
authors.initials: A
authors.lastname: De Maio
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000502:physiology*; D013156:Splenectomy; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10