Korean J Crit Care Med.  2010 Sep;25(3):149-154. 10.4266/kjccm.2010.25.3.149.

The Effect of Itraconazole Pretreatment in Lipopolysaccharide-Induced Acute Lung Injury in Rats

• Shin TR
• Lee YM
• Koh Y

• KMID: 2228198
• DOI: http://doi.org/10.4266/kjccm.2010.25.3.149

Abstract

BACKGROUND
Despite the fact that a randomized controlled trial did not support the use of ketoconazole for treatment of acute lung injury (ALI), there is evidence that pretreatment with ketoconazole might prevent ALI in critically ill patients. An in vitro study showed, however, that itraconazole was a more potent inhibitor of thromboxane and leukotriene formation than was ketoconazole. We investigated the effect of itraconazole pretreatment in lipopolysaccharide (LPS)-induced ALI in rats.
METHODS
Twenty-one pathogen free, male Sprague-Dawley rats were administered either saline or LPS (5 mg/kg of body weight) intratracheally, with or without intraperitoneal pretreatment of itraconazole (2.5 mg/kg). Six hours after saline or LPS treatment (7 h after itraconazole pretreatment), samples were obtained.
RESULTS
Compared with the saline group, LPS group had increased total cell count, polymorphonuclear leukocyte differential count, protein, lactate dehydrogenase (LDH) and cytokines in BAL fluid. Itraconazole pretreatment decreased polymrphonuclear leukocyte differential count, protein and LDH in BAL fluid compared with those of LPS-treated rats without itraconazole pretreatment. Itraconazole pretreatment also decreased the elevated BAL fluid levels of interleukin-1beta (IL-1beta) and cytokine-induced neutrophil chemoattractant (CINC) by LPS. There was, however, no difference in the BAL fluid tumor necrosis factor alpha (TNF-alpha) level in terms of itraconazole pretreatment in LPS-treated rats. Histopathologic features of LPS-induced ALI were attenuated by itraconazole pretreatment.
CONCLUSIONS
These results suggest that itraconazole pretreatment attenuated LPS-induced ALI in rats. Decreases in levels of IL-1beta and CINC would likely be associated with attenuation of LPS-induced ALI in rats by itraconazole pretreatment.

Keyword

acute lung injury; cytokine; itraconazole; lipopolysaccharide

MeSH Terms

Acute Lung Injury
Animals
Cell Count
Critical Illness
Cytokines
Humans
Interleukin-1beta
Itraconazole
Ketoconazole
L-Lactate Dehydrogenase
Leukocytes
Male
Neutrophils
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-1beta
Itraconazole
Ketoconazole
L-Lactate Dehydrogenase
Tumor Necrosis Factor-alpha