title: Mild hypothermia reduces expression of heat shock protein 60 in leukocytes from severely head-injured patients.
abstract: BACKGROUND
  Infectious complications are among the most serious problems that occur in severely head-injured patients treated with mild hypothermia. The mechanism underlying the susceptibility to infection has not been clarified. Heat shock protein (HSP) 60 has been reported to play an essential role in innate immunity. Thus, we conducted a study to clarify the impact of mild hypothermia on the expression of HSPs in polymorphonuclear leukocytes (PMNLs) in severely head-injured patients.
  
  
  METHODS
  Between September 1997 and November 1999, 17 severely head-injured patients with a Glasgow Coma Scale score of 8 or less at admission in whom intracranial pressure could be maintained below 20 mm Hg by conventional therapy were randomly assigned to two treatment groups: a mild hypothermia group (HT group, nine patients) and a normothermia group (NT group, eight patients). The HT group was subjected to mild hypothermia (intracranial temperature, 34 degrees C) for 48 hours followed by rewarming at a rate of 1 degrees C per day for 3 days, whereas the NT group was subjected to normothermia (intracranial temperature, 37 degrees C) for 5 days. Blood samples were serially obtained at three time points; days 0 to 1, days 2 to 5, and days 6 to 14 after head injury. We measured the expression of HSP27, HSP60, HSP70, and HSP90 by flow cytometry.
  
  
  RESULTS
  The two groups were similar with respect to prognostic factors, and there was no difference in clinical outcome. The expression of PMNL HSP60 in the HT group was significantly lower in all three time periods compared with that in the NT group (p < 0.05), whereas expression of the other HSPs did not differ significantly between the groups. The incidence of infectious complications was significantly increased in the HT group over that in the NT group (p < 0.05). In in vitro studies, PMNLs from 10 healthy volunteers were incubated at 37 degrees C, 34 degrees C, or 26 degrees C for 1 hour with sodium arsenite (100 micromol/L), an HSP inducer. The expression of HSP60 at 26 degrees C and 34 degrees C was significantly lower than that at 37 degrees C (p < 0.05), whereas expression of the other HSPs did not differ significantly at 26 degrees C, 34 degrees C, or 37 degrees C.
  
  
  CONCLUSIONS
  Mild hypothermia reduces the expression of HSP60 in PMNLs from severely head-injured patients. Thus, mild hypothermia may suppress innate immunity.
authors.affiliation: Department of Traumatology and Critical Care Medicine, Tottori Prefectural General Hospital, Japan. hashiguchi@mx51.tiki.ne.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hashiguchi
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Shiozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Taichin
authors.initials: T
authors.lastname: Koh
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Noborio
authors.forename: Keiko
authors.initials: K
authors.lastname: Fugita
authors.forename: Pavel
authors.initials: P
authors.lastname: Akimau
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kuwagata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimazu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugimoto
mesh_terms: D000293:Adolescent; D000328:Adult; D020208:Brain Injury, Chronic / Q000209:etiology; D018834:Chaperonin 60 / Q000032:analysis* / Q000276:immunology; D006259:Craniocerebral Trauma / Q000150:complications / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods*; D007108:Immune Tolerance / Q000276:immunology; D007239:Infections / Q000209:etiology; D015601:Injury Severity Score; D019586:Intracranial Hypertension / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry* / Q000276:immunology; D018579:Patient Selection; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018834:Chaperonin 60