Gm. Matuschak et al., UP-REGULATION OF POSTBACTEREMIC TNF-ALPHA AND IL-1-ALPHA GENE-EXPRESSION BY ALVEOLAR HYPOXIA REOXYGENATION IN PERFUSED RAT LUNGS/, American journal of respiratory and critical care medicine, 157(2), 1998, pp. 629-637
Citations number
35
Categorie Soggetti
Emergency Medicine & Critical Care","Respiratory System
Decreases in the alveolar O-2 tension commonly follow gram-negative ba
cteremic shock that progresses to the acute respiratory distress syndr
ome (ARDS). To examine the effects of alveolar hypoxia and reoxygenati
on (H/R) on postbacteremic pulmonary cytokine expression, lungs from S
prague-Dawley rats (n = 43) were perfused over 180 min after hematogen
ous infection with 10(9) live Escherichia coli serotype 055:B5 (EC) or
infusion of 0.9% NaCl (NS). Compared with normoxic EC and NS controls
, EC + H/R and NS + H/R lungs received 90 min of constant-flow hypoxia
followed by 60 min of reoxygenation. Perfusates were cultured and ana
lyzed for TNF-alpha, IL-1 alpha, IL-1 beta, and PGE(2) while monitorin
g pulmonary artery pressure (Ppa). Changes in the filtration coefficie
nt (K-f) were evaluated at 180 min when cytokine mRNA levels were asse
ssed in lung homogenates. Transcripts of the anti-inflammatory cytokin
e TGF-beta 1 and of inducible cyclooxygenase (COX-2) were similarly an
alyzed. For equivalent EC clearance, Ppa, and K-f as in normoxic EC, p
ostbacteremic H/R increased TNF-alpha gene expression and doubled the
export of TNF-alpha from the lungs, an effect not blocked by allopurin
ol. IL-1 alpha transcripts were also increased in EC + H/R versus EC l
ungs, in contrast to the lack of change in IL-1 beta, TGF-beta, or COX
-2 mRNA levels, or in cell-associated or circulating IL-1 beta and PGE
(2). Thus, gram-negative bacteremic lung infection and secondary alveo
lar H/R upregulate the expression of specific inflammatory cytokines c
ompared with pulmonary infection under normoxic conditions, independen
tly of xanthine oxidase-induced O-2 radicals. These findings identify
the alveolar Po-2 as a potent immunomodulatory signal whose reductions
early after gram-negative sepsis may enhance lung inflammation in ARD
S.