A role of neutrophils in the down-regulation of IL-6 and CD14 following hemorrhagic shock.
Hemorrhagic shock (HS) followed by resuscitation has been shown to initiate a series of events, including local cytokine production and PMN accumulation. To determine whether PMN are involved in the regulation of IL-6 expression in the liver or lungs, IL-6 mRNA levels were measured in rats made neutropenic by vinblastine pretreatment prior to HS. IL-6 mRNA levels were determined at 4 or 24 h following resuscitation from shock. Vinblastine alone in normal rats or sham-treated rats had no effect at 4 or 24 h. Vinblastine pretreatment had no effect on the HS-induced increase in IL-6 mRNA at 4 h but dramatically increased levels in both liver and lung at 24 h. Peripheral PMN counts were reduced by 95% in all vinblastine-treated animals. Similar changes seen in CD14 mRNA expression indicate that these effects are not limited to IL-6. These data show that normal PMN levels are not needed for induction of IL-6 and CD14 in HS, and suggest that PMN accumulation down-regulates the expression of these genes.
Omert
L
L
Department of Surgery, University of Pittsburgh, Pennsylvania 15261, USA.
Tsukada
K
K
Hierholzer
C
C
Lyons
V A
VA
Carlos
T M
TM
Peitzman
A B
AB
Billiar
T R
TR
D000818:Animals; D015536:Down-Regulation; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014747:Vinblastine / Q000494:pharmacology
D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D014747:Vinblastine