Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.

Abstract

INTRODUCTION:

Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS) and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury), intraperitoneal (IP) endotoxin administration (indirect lung injury) and, for comparison, intratracheal (IT) endotoxin administration (direct lung injury) with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation.

METHODS:

Bronchoalveolar cytokines (IL-6, CXCL1, TNF-α, IL-1β, and IL-10), BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [a biochemical marker of neutrophil infiltration]), and serum cytokines were determined in adult male C57Bl/6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping), IP endotoxin (10 µg), or IT endotoxin (80 µg) with and without intratracheal (IT) IL-6 (25 ng or 200 ng) treatment.

RESULTS:

Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin.

CONCLUSION:

IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of ARDS.

• Authors: Rhea Bhargava, William Janssen, Christopher Altmann, Ana Andrés-Hernando, Kayo Okamura, R William Vandivier, Nilesh Ahuja, Sarah Faubel
• Journal: PloS one (PLoS One) Vol. 8 Issue 5 Pg. e61405 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23667439 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Endotoxins
• Interleukin-6
• endotoxin, Escherichia coli
• Creatinine

Topics

• Acute Kidney Injury (complications)
• Acute Lung Injury (etiology, metabolism)
• Analysis of Variance
• Animals
• Blood Urea Nitrogen
• Bronchoalveolar Lavage Fluid (immunology)
• Creatinine (blood)
• Cytokines (immunology)
• Endotoxins (toxicity)
• Interleukin-6 (blood, immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Pneumonia (etiology, metabolism)
• Trachea (metabolism)