Biotherapy

, Volume 7, Issue 3–4, pp 195–210

Cytokines in the treatment of fungal infections

  • Bart -Jan Kullberg
  • Jan W. van 't Wout
Article

Abstract

The incidence of invasive fungal infections in the immunocompromized host 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 potential to augment host resistance and as adjunctive therapy of invasive mycoses. We discuss the mechanisms of host defense against invasive candidiasis, aspergillosis, and cryptococcosis, and review the use of cytokines and growth factors in this setting. Interleukin-1 has been shown effective in an animal model of disseminated candidiasis, even during severe granulocytopenia. Interferon-γ has been very effective as a modulator of resistance against a variety of fungal infectionsin vitro. The effect of interferon-γ against disseminated candidiasis has been demonstrated in a mouse model. Activation of neutrophils is the main mechanism by which interferon-γ enhances the elimination ofCandida, and consequently the agent is not effective in severly granulocytopenic animals. Data on the role of colony-stimulating factors against fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now being performed.

Key words

Invasive mycoses Candida, Aspergillus host defense immunotherapy interferon interleukin tumor necrosis factor colony-stimulating factors 

Abbreviations

CGD

chronic granulomatous disease

G-CSF

granulocyte colony-stimulating factor

M-CSF

monocyte colony-stimulating factor

GM-CSF

granulocyte-monocyte colony-stimulating factor

IFN-γ

interferon-gamma

IL

interleukin

LAK

lymphokine-activated killer

LPS

lipopolysaccharide

MDP

muramyl dipeptide

NK

natural killer

PMN

polymorphonuclear leukocytes

rh

recombinant human

ROI

reactive oxygen intermediates

TNF

tumor necrosis factor

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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Bart -Jan Kullberg
    • 1
    • 2
  • Jan W. van 't Wout
    • 1
    • 2
  1. 1.Department of MedicineUniversity Hospital NijmegenThe Netherlands
  2. 2.Department of Infectious DiseasesUniversity Hospital LeidenThe Netherlands

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