title: Role of interleukin 1 receptor like 1 (ST2) in gram-negative and gram-positive sepsis in mice.
abstract: BACKGROUND
  Interleukin 1 receptor-like 1 (ST2) has been implicated as a negative regulator of Toll-like receptor signaling. We here sought to elucidate the role of ST2 in cytokine release and systemic infection caused by two common human sepsis pathogens, Streptococcus pneumoniae (gram-positive) and Klebsiella pneumoniae (gram-negative).
  
  
  METHODS
  Whole blood leukocytes and splenocytes were harvested from ST2-deficient (st2) and wild-type (WT) mice and stimulated ex vivo with S. pneumoniae or K. pneumoniae. In addition, st2 and WT mice were infected intravenously with these bacteria, and bacterial loads and cytokine levels were measured in blood, spleens and lungs at 6, 24, and 48 h thereafter.
  
  
  RESULTS
  Unexpectedly, st2 blood leukocytes and splenocytes produced lower levels of cytokines and chemokines than WT cells in response to either pathogen. In contrast, the in vivo role of ST2 during sepsis caused by these bacteria was limited, although at 6 and 24 h after infection with S. pneumoniae bacterial loads were lower in spleens of st2 mice.
  
  
  CONCLUSIONS
  ST2 augments rather than inhibits cytokine release by blood leukocytes and splenocytes exposed to S. pneumoniae or K. pneumoniae, but plays a limited role in host defense during sepsis caused by these pathogens.
authors.affiliation: *Center of Experimental and Molecular Medicine, Center of Infection and Immunity Amsterdam, †Department of Pathology, and ‡Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Blok
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D000072179:Interleukin-1 Receptor-Like 1 Protein; D007710:Klebsiella Infections / Q000150:complications / Q000503:physiopathology*; D007711:Klebsiella pneumoniae; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000503:physiopathology*; D018123:Receptors, Interleukin / Q000502:physiology*; D018805:Sepsis / Q000150:complications / Q000503:physiopathology*
chemical_list: D016207:Cytokines; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018123:Receptors, Interleukin