TH1 AND TH2 CYTOKINES IN MICE WITH INVASIVE ASPERGILLOSIS

With a murine model of invasive aspergillosis we investigated cytokine production by CD4(+) T helper cells and the effects of cytokine admin istration or neutralization on the course and outcome of infection. Pa tterns of susceptibility and resistance to infection were obtained wit h different strains of mice injected with different inocula of Aspergi llus fumigatus conidia. Mice surviving the primary infection also resi sted a subsequent lethal infection that was associated with production of gamma interferon by CD4(+) T splenocytes. Impaired neutrophil anti fungal activity, observed in susceptible mice, was concomitant with a predominant production of interleukin-4 (IL-4) by CD4(+) splenocytes. In these mice, exogenous administration of IL-12 failed to induce resi stance to infection; in contrast, treatment with soluble IL-4 receptor cured more than 70% of the mice from primary infection and resulted i n the onset of acquired resistance to a subsequent lethal infection. T hese findings indicate that in murine invasive aspergillosis, producti on of IL-4 by CD4(+) T cells may be one major factor discriminating su sceptibility and resistance to infection.