Treatment of Murine Pulmonary Cryptococcosis with a Combination of Fluconazole and Interleukin-12

Abstract

Interleukin-12 (IL-12) is known to protect the host from various pathogens by inducing cell-mediated immunity. In a murine model of pulmonary infection withCryptococcus neoformans, the daily administration of 0.1 μg/day of IL-12 for 7 day failed to protect mice from infection when treatment commenced 7 days after intratracheal instillation of the pathogen. However, IL-12 administered prophylactically or on the day of infection was effective in combating the infection. Because the number of yeast cells increase by 10-fold in the lungs within a short period of time, and in an attempt to control the growth of the fungus, a combination therapy of an antifungal agent, fluconazole (FCZ), and IL-12 was initiated 7 days after infection. Treatment with FCZ significantly prolonged survival time, and when combined with IL-12, there was a further prolongation of survival time. In addition, administration of both agents significantly reduced the number of live microorganisms isolated from the lung tissue. Our results suggest that the combined use of FCZ and IL-12 may represent a new therapeutic strategy for cryptococcal infections in patients with impaired cell-mediated immunity.