Effect of endogenous nitric oxide on hyperoxia and tumor necrosis factor-alpha-induced leukosequestration and proinflammatory cytokine release in rat airways.

Abstract

OBJECTIVE:

To investigate the effects of endogenous nitric oxide on hyperoxia and tumor necrosis factor-alpha-induced leukosequestration and proinflammatory cytokine release in rat airways.

DESIGN:

Prospective, randomized, controlled animal study.

SETTING:

Experimental laboratory.

SUBJECTS:

Male Sprague-Dawley rats weighing 350-500 g.

INTERVENTIONS:

The rats were pretreated with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) or saline intravenously 4-6 mins before intratracheal administration of tumor necrosis factor-alpha, 95% oxygen, or both, when the vasopressor effect of L-NAME had reached a plateau.

MEASUREMENTS AND MAIN RESULTS:

Bronchoalveolar lavage fluid was recovered from the airway of rats after exposure to 95% oxygen and tumor necrosis factor-alpha for 6 hrs under ventilator support. Neutrophils in lavage fluid were isolated and examined for the inducible nitric oxide synthase expression by flow-cytometric assay. Tumor necrosis factor-alpha and interleukin-1 beta in lavage fluid were measured by enzyme-linked immunosorbent assay. The percentage of neutrophils in bronchoalveolar fluid was significantly higher in rats exposed to hyperoxia + tumor necrosis factor-alpha (29.7 +/- 12.5%) compared with rats with hyperoxia (16.3 +/- 1.2%), tumor necrosis factor-alpha (4.2 +/- 1.1%), or room air (5.0 +/- 1.8%) alone (p <.05). Rats exposed to hyperoxia + tumor necrosis factor-alpha had significantly higher concentrations of inducible nitric oxide synthase of neutrophils (350.1 +/- 75.7 mean fluorescence intensity), compared with rats with hyperoxia (64.9 +/- 1.6 mean fluorescence intensity), tumor necrosis factor-alpha (102.6 +/- 15.3 mean fluorescence intensity), or room air (111.2 +/- 25.8 mean fluorescence intensity) alone (p <.05). Rats exposed to hyperoxia + tumor necrosis factor-alpha significantly produced higher concentrations of tumor necrosis factor-alpha and interleukin-1 beta, compared with rats with tumor necrosis factor-alpha, hyperoxia, or room air alone. Hyperoxia + tumor necrosis factor-alpha also significantly increased growth-related oncogene/cytokine-induced neutrophil chemoattractant (GRO/CINC)-1 in bronchoalveolar fluid, compared with those receiving tumor necrosis factor-alpha alone, hyperoxia alone, or room air alone. L-NAME significantly enhanced the percentage of neutrophil recovery and the production of tumor necrosis factor-alpha, interleukin-1 beta, and GRO/CINC-1 in airways compared with the corresponding hyperoxia + tumor necrosis factor-alpha treatment alone.

CONCLUSIONS:

Endogenous nitric oxide may be an important endogenous inhibitor of hyperoxia + tumor necrosis factor-alpha-induced leukocyte recruitment and subsequently tumor necrosis factor-alpha, interleukin-1 beta, and GRO/CINC-1 release.

• Authors: Horng-Chyuan Lin, Chun-Hua Wang, Chih-Teng Yu, Kuo-Shiung Huang, Chien-Ying Liu, Chih-Wei Yang, Han-Pin Kuo
• Journal: Critical care medicine (Crit Care Med) Vol. 31 Issue 2 Pg. 508-16 (Feb 2003) ISSN: 0090-3493 [Print] United States
• PMID: 12576959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Tumor Necrosis Factor-alpha
• Nitric Oxide

Topics

• Animals
• Cytokines (metabolism)
• Hyperoxia (immunology)
• Male
• Neutrophils (immunology)
• Nitric Oxide (physiology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (physiology)