IL-12 Protects Mice Against Pulmonary and Disseminated Infection Caused by Cryptococcus Neoformans

Clin Exp Immunol. 1996 May;104(2):208-14. doi: 10.1046/j.1365-2249.1996.14723.x.

Abstract

We examined the role of IL-12 in host resistance to Cryptococcus neoformans using a murine model of pulmonary and disseminated infection. In this model, mice were infected intratracheally with viable yeast cells. Mice untreated with IL-12 allowed an uncontrolled multiplication of yeast cells in the lung with infiltrations of few inflammatory cells, and a cryptococcal dissemination to the brain and meningitis by 3 weeks, resulting in death of all animals within 4-6 weeks. IL-12, when administered from the day of tracheal infection for 7 days, induced a marked infiltration of inflammatory cells, consisting mostly of mononuclear cells, and significantly reduced the number of viable yeast cells in the lung. The treatment suppressed brain dissemination, as shown by a marked reduction of yeast cells in the brain and prevention of meningitis. These effects resulted in a significant increase in the survival rate of infected mice. In contrast, late administration of IL-12 commencing on day 7 after instillation of yeast cells failed to protect the mice against infection with C. neoformans. In further experiments, early administration of IL-12 markedly induced interferon-gamma (IFN-gamma) mRNA in the lungs of infected mice, while no IFN-gamma mRNA was detected without this treatment. Our results indicate that IL-12 is effective when administered in the early period of pulmonary cryptococcal infection.

MeSH terms

  • Animals
  • Base Sequence
  • Cryptococcosis / mortality
  • Cryptococcosis / pathology
  • Cryptococcosis / prevention & control*
  • Cryptococcus neoformans / drug effects
  • Cryptococcus neoformans / growth & development
  • Female
  • Interferon-gamma / genetics
  • Interleukin-12 / therapeutic use*
  • Lung / metabolism
  • Lung Diseases, Fungal / mortality
  • Lung Diseases, Fungal / pathology
  • Lung Diseases, Fungal / prevention & control*
  • Meningitis, Cryptococcal / mortality
  • Meningitis, Cryptococcal / pathology
  • Meningitis, Cryptococcal / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Molecular Sequence Data
  • RNA, Messenger / biosynthesis

Substances

  • RNA, Messenger
  • Interleukin-12
  • Interferon-gamma