Xanthine oxidase-derived oxygen radicals increase lung cytokine expression in mice subjected to hemorrhagic shock.
Acute inflammatory lung injury often complicates hemorrhagic shock, a systemic ischemia-reperfusion syndrome. Because oxygen radicals are generated during ischemia-reperfusion, and oxygen radicals can activate nuclear regulatory factors that affect transcription of proinflammatory cytokines, we examined the premise that oxygen radicals increase interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) expression in lung mononuclear cells after hemorrhage. Intraparenchymal pulmonary mononuclear cells isolated 1 h after hemorrhage from control mice had increased levels of mRNA for IL-1 beta (P < 0.001) and TNF-alpha (P < 0.05) compared with cells from sham-hemorrhaged mice. Hemorrhaged mice treated with the oxygen radical scavenger dimethylthiourea (DMTU) had decreased levels of mRNA for IL-1 beta in pulmonary mononuclear cells, compared with hemorrhaged controls (P < 0.05). In hemorrhaged mice depleted of xanthine oxidase (XO) by a tungsten-enriched diet, pulmonary mononuclear cell mRNA levels for IL-1 beta and TNF-alpha were significantly decreased (P < 0.01 and 0.05, respectively), compared with cells from hemorrhaged control mice fed a normal diet. Similarly, mRNA transcripts for IL-1 beta and TNF-alpha among pulmonary mononuclear cells from hemorrhaged mice treated with allopurinol, an inhibitor of XO, were also significantly reduced (P < 0.05 and 0.001, respectively), compared with hemorrhaged control mice not treated with allopurinol. Our results indicate that XO-derived oxygen radicals contribute to the increased expression of mRNA for IL-1 beta and TNF-alpha, which occurs among pulmonary mononuclear cell populations immediately after hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwartz
M D
MD
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Repine
J E
JE
Abraham
E
E
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014414:Tungsten / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016207:Cytokines; D017382:Reactive Oxygen Species; D000493:Allopurinol; C038983:1,3-dimethylthiourea; D014969:Xanthine Oxidase; D013890:Thiourea; D014414:Tungsten