title: IL-2 regulates SEB induced toxic shock syndrome in BALB/c mice.
abstract: BACKGROUND
  Toxic Shock Syndrome (TSS) is characterized by fever, rash, hypotension, constitutional symptoms, and multi-organ involvement and is caused by Staphylococcus aureus enterotoxins such as Staphylococcal Enterotoxin B (SEB). SEB binds to the MHC-IIalpha chain and is recognized by the TCRbeta chain of the Vbeta8 TCR(+) T cells. The binding of SEB to Vbeta chain results in rapid activation of T cells and production of inflammatory cytokines, such as Interleukin-2 (IL-2), Interferon-gamma and Tumor Necrosis Factor-alpha which mediate TSS. Although IL2 was originally identified as the T cell growth factor and was proposed to contribute to T cell differentiation, its role in TSS remains unexplored.
  
  
  RESULTS
  Mice were injected with D-Gal (25 mg/mouse). One hour after D-Galactosamine (D-Gal) injection each mouse was injected with SEB (20 microg/mouse. Mice were then observed for 72 hrs and death was recorded at different times. We tested Interleukin-12, IFNgamma, and IL-2 deficient mice (IL-2(-/-)), but only the IL-2 deficient mice were resistant to SEB induced toxic shock syndrome. More importantly reconstitution of IL-2 in IL-2 deficient mice restored the shock. Interestingly, SEB induced IL-2 production from T cells was dependent on p38MAPK activation in macrophages as inhibition of it in macrophages significantly inhibited IL-2 production from T cells.
  
  
  CONCLUSIONS
  This study shows the importance of IL -2 in TSS which has not been previously explored and it also shows that regulating macrophages function can regulate T cells and TSS.
authors.affiliation: Washington University in St. Louis, St. Louis, Missouri, United States of America. khana@vision.wustl.edu
authors.forename: Aslam Ali
authors.initials: AA
authors.lastname: Khan
authors.forename: Shilpee
authors.initials: S
authors.lastname: Priya
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Saha
mesh_terms: D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology; D004768:Enterotoxins / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000172:deficiency; D018664:Interleukin-12 / Q000172:deficiency; D007376:Interleukin-2 / Q000172:deficiency / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D012772:Shock, Septic / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D004768:Enterotoxins; D007093:Imidazoles; D007376:Interleukin-2; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580