CYTOKINES IN THE TREATMENT OF FUNGAL-INFECTIONS

The incidence of invasive fungal infections in the immunocompromized h ost has increased during the past decade. Even the recently developed antifungal drugs are unable to cure these infections in patients with severely impaired host defense mechanisms. Cytokines have great potent ial to augment host resistance and as adjunctive therapy of invasive m ycoses. We discuss the mechanisms of host defense against invasive can didiasis, aspergillosis, and cryptococcosis, and review the use of cyt okines and growth factors in this setting. Interleukin-1 has been show n effective in an animal model of disseminated candidiasis, even durin g severe granulocytopenia. Interferon-gamma has been very effective as a modulator of resistance against a variety of fungal infections in v itro. The effect of interferon-gamma against disseminated candidiasis has been demonstrated in a mouse model. Activation of neutrophils is t he main mechanism by which interferon-gamma enhances the elimination o f Candida, and consequently the agent is not effective in severly gran ulocytopenic animals. Data on the role of colony-stimulating factors a gainst fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now bein g performed.