Therapeutic hypercapnia enhances the inflammatory response to endotoxin in the lung of spontaneously breathing rats.

Abstract:

OBJECTIVE:To test the hypothesis that therapeutic hypercapnia enhances the proinflammatory responses to endotoxemia in the lung and spleen of rats. DESIGN:Prospective randomized study. SETTINGS:Hospital research institute. SUBJECTS:Forty-eight adult male rats. INTERVENTIONS:Rats were randomly assigned for a 24-hr period to four breathing groups (n = 11/group), including air (controls), normoxic air with 5% CO2 (therapeutic hypercapnia), air and endotoxemia (5 mg/kg endotoxin), and therapeutic hypercapnia with endotoxemia. After euthanasia, the lung and spleen were removed for pro- and anti-inflammatory cytokine analyses and pulmonary histology evaluation. Four additional rats were used to examine changes in gas exchange and acid-base balance during exposure to therapeutic hypercapnia with and without endotoxemia before and at 4, 12, and 24 hrs into the study, using a permanently catheterized femoral artery. MEASUREMENTS AND MAIN RESULTS:The ratios of proinflammatory cytokines (interleukin-1β [IL-1β] and IL-6) and an anti-inflammatory cytokine (IL-10) in the lungs and spleen were used as indices of inflammatory status. The wet-weight to dry-weight ratios, histologic changes in lung interstitial inflammation, and alveolar structures were used as indices of endotoxin-induced acute lung injury. IL-1β and IL-6 expression was significantly high in the lung of therapeutic hypercapnia-treated endotoxemic rats compared to the lung of rats subjected to only endotoxemia (p < .05 and p < .001, respectively). In the spleen, therapeutic hypercapnia-treated endotoxemic rats had low expression of IL-1β and IL-6 compared to rats subjected to only endotoxemia (p > .05 and p < .001). Therapeutic hypercapnia following endotoxemic challenge was associated with a proinflammatory response in the lung and an anti-inflammatory response in spleen, as assessed by the ratios of IL-1β and IL-6 to IL-10. The wet-weight to dry-weight ratio and the interstitial space were significantly increased only in therapeutic hypercapnia-treated endotoxemic rats (p < .05). The alveolar-septal thickness was significantly increased by 21% in endotoxemic rats (p < .001) and by 33% in therapeutic hypercapnia-treated endotoxemic rats (p < .001). CONCLUSIONS:A 24-hr exposure to therapeutic hypercapnia in endotoxin-stimulated, spontaneously breathing rats is associated with a proinflammatory immune response in the lung and anti-inflammatory response in the spleen as well as an increase in certain histologic indices of endotoxin-induced lung injury.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

Norozian FM,Leoncio M,Torbati D,Meyer K,Raszynski A,Totapally BR

doi

10.1097/CCM.0b013e31820ee1f2

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

1400-6

issue

6

eissn

0090-3493

issn

1530-0293

pii

00003246-201106000-00025

journal_volume

39

pub_type

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