Proinflammatory cytokine levels in lungs predict long-term survival in two murine pulmonary aspergillosis models following anti-fungal drug therapy

J. A. Olson, D. J. Hahka, N. Y. Nguyen and J. P. Adler-Moore

Author address: 

Cal Poly University, USA

Abstract: 

Background: Pulmonary aspergillosis causes extensive necrosis and hemorrhage in the lungs with several reports of elevated proinflammatory cytokine levels in infected animals. Given the potential toxic side effects associated with high levels of proinflammatory cytokines, we used two murine aspergillosis models in the present study to determine if cytokine levels in the serum or lung early in the treatment could be used to predict antifungal treatment outcome at study end. Materials and methods: Swiss Webster mice (n = 7/gp for lung tissue, n = 8/gp for survival) were given 6 mg kg)1 triamcinolone acetonide IP on days )3, 0 and +2 and challenged intranasally d0 with 5.4 · 10ex7 Aspergillus fumigatus (Afum) or 4.1 · 10ex6 Aspergillus flavus (Afla) conidia. IV treatment was begun 2 h post-challenge and continued for 4 days. Afum infected mice were given 10 mg kg)1 liposomal amphotericin B (L-AmB), control liposomes without drug (ConL), or 5% dextrose (D5W). Afla infected mice were given 10 mg kg)1 L-AmB, 10 mg kg)1 Caspofungin (Cas), 10 mg kg)1 L-AmB + 10 mg kg)1 Cas, or D5W. At 98 h (Afum) or 26 h(Afla) post-challenge, blood and lungs were collected for both cytokine analysis and lung fungal burden (Log10 cfu); remaining mice were monitored for morbidity to d + 21. Results: With Afum infection, survival at d + 21 was significantly higher with L-AmB (75%) vs. D5W or ConL (25%) (P = 0.024) while lung cytokine levels of IL-6, TNF-alpha, IL-12, and gamma inteferon at d + 4 were significantly lower with L-AmB vs. D5W or ConL (P ≤ 0.02). Afum Log10 cfu in the lungs was also significantly lower
2011

abstract No: 

O4.5

Full conference title: 

Trends in Medical Mycology, 5th
    • TIMM 5th (2013)