title: Activation of regulatory T cells during inflammatory response is not an exclusive property of stem cells.
abstract: BACKGROUND
  Sepsis and systemic-inflammatory-response-syndrome (SIRS) remain major causes for fatalities on intensive care units despite up-to-date therapy. It is well accepted that stem cells have immunomodulatory properties during inflammation and sepsis, including the activation of regulatory T cells and the attenuation of distant organ damage. Evidence from recent work suggests that these properties may not be exclusively attributed to stem cells. This study was designed to evaluate the immunomodulatory potency of cellular treatment during acute inflammation in a model of sublethal endotoxemia and to investigate the hypothesis that immunomodulations by cellular treatment during inflammatory response is not stem cell specific.
  
  
  RESULTS
  Endotoxemia was induced via intra-peritoneal injection of lipopolysaccharide (LPS) in wild type mice (C3H/HeN). Mice were treated with either vital or homogenized amniotic fluid stem cells (AFS) and sacrificed for specimen collection 24 h after LPS injection. Endpoints were plasma cytokine levels (BD™ Cytometric Bead Arrays), T cell subpopulations (flow-cytometry) and pulmonary neutrophil influx (immunohistochemistry). To define stem cell specific effects, treatment with either vital or homogenized human-embryonic-kidney-cells (HEK) was investigated in a second subset of experiments. Mice treated with homogenized AFS cells showed significantly increased percentages of regulatory T cells and Interleukin-2 as well as decreased amounts of pulmonary neutrophils compared to saline-treated controls. These results could be reproduced in mice treated with vital HEK cells. No further differences were observed between plasma cytokine levels of endotoxemic mice.
  
  
  CONCLUSIONS
  The results revealed that both AFS and HEK cells modulate cellular immune response and distant organ damage during sublethal endotoxemia. The observed effects support the hypothesis, that immunomodulations are not exclusive attributes of stem cells.
authors.affiliation: Center of Pediatric Surgery Hannover, Hannover Medical School and Bult Children's Hospital, Hannover, Germany. gosemann.jan@mh-hannover.de
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Gosemann
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Kuebler
authors.forename: Michela
authors.initials: M
authors.lastname: Pozzobon
authors.forename: Claudia
authors.initials: C
authors.lastname: Neunaber
authors.forename: Julia H K
authors.initials: JH
authors.lastname: Hensel
authors.forename: Marco
authors.initials: M
authors.lastname: Ghionzoli
authors.forename: Paolo
authors.initials: P
authors.lastname: de Coppi
authors.forename: Benno M
authors.initials: BM
authors.lastname: Ure
authors.forename: Gesine
authors.initials: G
authors.lastname: Holze
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000209:etiology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D056747:Immunomodulation; D007376:Interleukin-2 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000166:cytology; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D008070:Lipopolysaccharides