title: Timing of hyperthermic preconditioning affects islet resistance against inflammation.
abstract: BACKGROUND
  Heat exposure of isolated islets enhances resistance against inflammation but decreases islet graft function. In contrast, donor preconditioning by whole-body hyperthermia increases islet ischemic tolerance and improves viability of pancreatic isografts. This study aimed to compare yield, viability, and inflammatory resistance of rat islets subjected to heat shock prior to (pre-HS) or after isolation (post-HS).
  
  
  METHODS
  Islets were isolated as previously described. HS (42 degrees C/45 min) was induced 12 hours before islet isolation (pre-HS, n = 31) or in freshly isolated islets prior to 12 hours of recovery at 37 degrees C (post-HS, n = 12). Islets continuously incubated at 37 degrees C served as controls (n = 33). Proinflammatory treatment included incubation with 0.05 mmol/L H(2)O(2), 1.0 mmol/L DETA-NO or cytokines (interleukin-1beta + tumor necrosis factoralpha + interferongamma).
  
  
  RESULTS
  Purified islet yield was 1200 +/- 80 IEQ in unconditioned donors (n = 45) and 980 +/- 80 IEQ after pre-HS (ns). Islet viability was not affected by post-HS, but the glucose stimulation index (P < 0.001, P < 0.01) and formazan production (P < 0.05) were significantly lower compared to pre-HS or sham treatment. The expression of heat shock protein HSP70 in pre-HS islets was slightly higher compared to controls (ns) but lower compared to post-HS islets (P < 0.05), correlating with the resistance against H(2)O(2) and DETA-NO compared to post-HS islets (P < 0.05) or controls (ns). Cytokines did not affect mitochondrial formazan production.
  
  
  CONCLUSIONS
  The findings indicate that hyperthermic islet treatment is less harmful if performed in the native pancreatic environment. This beneficial effect is associated with a decreased HSP70 expression resulting in a reduced resistance against inflammatory mechanisms.
authors.affiliation: Third Medical Department, University Hospital, Giessen, Germany. Daniel.Brandhorst@innere.med.uni-giessen.de
authors.forename: D
authors.initials: D
authors.lastname: Brandhorst
authors.forename: M
authors.initials: M
authors.lastname: Olbrich
authors.forename: A
authors.initials: A
authors.lastname: Alt
authors.forename: R G
authors.initials: RG
authors.lastname: Bretzel
authors.forename: H
authors.initials: H
authors.lastname: Brandhorst
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D005334:Fever; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D007249:Inflammation / Q000517:prevention & control*; D019194:Ischemic Preconditioning / Q000379:methods*; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology*; D009926:Organ Preservation / Q000379:methods; D010179:Pancreas / Q000166:cytology; D051381:Rats
chemical_list: D018840:HSP70 Heat-Shock Proteins