Protective effects of heme-oxygenase expression against endotoxic shock: inhibition of tumor necrosis factor-alpha and augmentation of interleukin-10.
BACKGROUND
Heme-oxygenase (HO)-1 acts as an inducible defense against oxidative stress and could play an important role in inflammation models, providing protection against oxidative stress and systemic inflammatory response. The objective of this study was to improve the role of HO-1 on systemic inflammatory response in an endotoxic shock model.


METHODS
Five groups of animals were used: control group; lipopolysaccharide (LPS) group, animals received LPS 5 mg/kg; hemin + LPS group, animals received pretreatment with hemin, used to induce HO-1 expression; Zn-PP group, animals received Zn-PP, a specific inhibitor of HO-1 activity and hemin group. At the end of the experiment, tissue and blood samples were isolated for the measurement of HO-1 mRNA expression, biochemical measurements, and cytokine measurements.


RESULTS
HO-1 messenger RNA expression and protein were induced to a larger extent in LPS group in distal organs. Hemin pretreatment induced a significant decrease oxidative stress and tumor necrosis factor-alpha plasma levels with a significant increase of interleukin-10 plasma levels. Pulmonary injury was markedly limited after hemin. Onset of lethality in LPS group occurred at H6, and was delayed until H10 with hemin. Inhibition of HO-1 activity by Zn-PP administration abolished the beneficial effect of hemin-pretreatment.


CONCLUSIONS
Early HO-1 expression may modulate systemic inflammatory response and limit end-organ injury in endotoxic shock model.
Tamion
Fabienne
F
Institut National de la Santé et de la Recherche Médicale, Rouen University Hospital, Rouen, France. fabienne.tamion@chu-rouen.fr
Richard
Vincent
V
Renet
Sylvanie
S
Thuillez
Christian
C
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology / Q000627:therapeutic use; D016753:Interleukin-10 / Q000097:blood*; D007413:Intestinal Mucosa / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D011524:Protoporphyrins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C017803:zinc protoporphyrin; D006427:Hemin; D051547:Heme Oxygenase-1