title: Serum levels of cytokines correlate to donor chimerism and acute graft-vs.-host disease after haematopoietic stem cell transplantation.
abstract: BACKGROUND
  Some patients become full donor chimeras (DC) early after stem-cell transplantation (SCT), while others remain mixed chimeras for a longer time. Little is known about the mechanism behind these phenomena.
  
  
  METHODS
  Serum cytokine levels during conditioning and during the first month after SCT were analysed in 30 patients. Of the 21 patients who became full T-cell DC from the first analysed sample, 12 developed grade II-IV acute graft-vs.-host disease (GVHD) and the other nine, mild or no acute GVHD. Another nine patients were T-cell mixed chimeras (MC). All MC patients had no or mild acute GVHD.
  
  
  RESULTS
  During the pretransplant conditioning, DC patients had higher levels of tumour necrosis factor (TNF)-alpha and lower levels of transforming growth factor (TGF)-beta and interleukin (IL)-10, compared with MC patients. During the first week after SCT, lower levels of TGF-beta and IL-10 and higher levels of soluble Fas (sFas) were found in DC patients compared with MC patients. During the second and third weeks after SCT, increased levels of TNF-alpha, interferon (IFN)-gamma and sFas were found among DC patients compared with MC patients. Patients who developed moderate-to-severe acute GVHD had higher levels of TNF-alpha, IFN-gamma, IL-10 and sFas at 2 weeks post-SCT than in those with less GVHD. Patients homozygous for the TNFd microsatellite alleles 3 or 4 had significantly higher TNF-alpha levels during conditioning and more often developed acute GVHD grades II-IV.
  
  
  CONCLUSIONS
  These results indicate that an imbalance between pro-inflammatory and immune- modulating cytokines are involved in the development of chimerism and acute GVHD after allo-SCT. The Fas/FasL pathway is probably involved in the elimination of recipient cells leading to full donor chimerism.
authors.affiliation: Department of Clinical Immunology and Centre for Allogeneic Stem Cell Transplantation, Huddinge University Hospital, Stockholm, Sweden. mats.remberger@labmed.ki.se
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.forename: Marie
authors.initials: M
authors.lastname: Jaksch
authors.forename: Mehmet
authors.initials: M
authors.lastname: Uzunel
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes; D018183:Transplantation Chimera; D019014:fas Receptor / Q000097:blood
chemical_list: D016207:Cytokines; D019014:fas Receptor