title: Hypothermia increases interleukin-6 and interleukin-10 in juvenile endotoxemic mice.
abstract: OBJECTIVE
  To develop a juvenile mouse model to establish effects of in vivo hypothermia on expression of the inflammation-modulating cytokines tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-10. Although induced hypothermia is neuroprotective in some patients, the mechanisms of protection are not well understood and concerns remain over potential detrimental effects, particularly in the setting of infection. We previously showed that in vitro hypothermia increases production of tumor necrosis factor-alpha and interleukin-1beta in lipopolysaccharide-treated monocytes.
  
  
  METHODS
  : Laboratory investigation.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Juvenile (4-wk) male C57BL/6 mice.
  
  
  METHODS
  : Mice were given chlorpromazine to suspend thermoregulation and lipopolysaccharide to stimulate cytokine production. Core temperature was maintained at 32 degrees C or 37 degrees C for 6 hrs by adjusting environmental temperature. In separate experiments, lipopolysaccharide-treated mice were kept in a cooling chamber without chlorpromazine treatment.
  
  
  RESULTS
  Plasma and organs were collected for cytokine quantitation. Chlorpromazine-treated hypothermic mice had 2.3-fold and 1.8-fold higher plasma interleukin-6 and interleukin-10 levels at 6 hrs compared with identically treated normothermic mice (p < .05), whereas plasma tumor necrosis factor-alpha and interleukin-1beta were not significantly different at 2 hrs or 6 hrs. Liver tumor necrosis factor-alpha and interleukin-6 were significantly higher in hypothermic vs. normothermic mice, but lung and brain cytokines were not different. Lipopolysaccharide-treated mice kept in a cooling chamber without chlorpromazine treatment developed varying degrees of hypothermia with associated increases in plasma interleukin-6 and interleukin-10. A nonspecific marker of stress (plasma corticosterone) was not affected by hypothermia in lipopolysaccharide-treated mice.
  
  
  CONCLUSIONS
  Further studies are necessary to determine the mechanism and physiologic consequences of augmented systemic interleukin-6 and interleukin-10 expression during induced hypothermia.
authors: Department of Pediatrics, University of Virginia Children's Hospital, Charlottesville, VA, USA.
authors: Corrine R
authors: CR
authors: Stewart
authors: Jessica P
authors: JP
authors: Landseadel
authors: Matthew J
authors: MJ
authors: Gurka
authors: Karen D
authors: KD
authors: Fairchild
mesh_terms: D000818:Animals; D002746:Chlorpromazine / Q000031:analogs & derivatives / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects; D019446:Endotoxemia; D004731:Endotoxins; D006979:Hyperthermia, Induced; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009125:Muscle Relaxants, Central; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D009125:Muscle Relaxants, Central; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C054028:chlorproethazine; D002746:Chlorpromazine