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Infection and Immunity, December 1999, p. 6314-6320, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cytokine Profiles of AIDS Patients Are Similar to Those of Mice with Disseminated Cryptococcus neoformans Infection

Olivier Lortholary,1 Luce Improvisi,1 Naima Rayhane,2 Francoise Gray,3 Catherine Fitting,2 Jean Marc Cavaillon,2 and Francoise Dromer1,*

Unité de Mycologie1 and Unité d'Immuno-Allergie,2 Institut Pasteur, 75724 Paris Cedex 15, and Service d'Anatomie et de Cytologie Pathologiques, Hôpital Raymond Poincaré, 92380 Garches,3 France

Received 28 June 1999/Returned for modification 6 August 1999/Accepted 1 September 1999

Cryptococcosis is an hematogenously disseminated meningoencephalitis during which the relationship between the disease severity and the immune response remains unclear. We thus analyzed, by enzyme-linked immunosorbent assay, proinflammatory (tumor necrosis factor alpha [TNF-alpha ] and interleukin-6 [IL-6]) and anti-inflammatory (IL-10) cytokine levels in plasma at the time of diagnosis in 51 AIDS patients with culture-proven cryptococcosis. We used a murine model to determine the correlation between cytokine levels and fungal burden in blood and tissues and the kinetics of the immune response and of the formation of cerebral lesions. In AIDS patients, plasma TNF-alpha and IL-10, but not IL-6, levels were significantly higher in the case of fungemia or disseminated infection than in their absence, whereas the presence of meningitis had no influence on these levels. In mice, none of these cytokines were detected within the first day after inoculation. Later on, TNF-alpha and IL-10, but not IL-6, levels in plasma correlated significantly with the fungal burden in the blood and spleen but not the brain. In the brain, cytokine levels were low compared to those in other compartments, and tissue lesions and a degree of infection similar to those observed in humans were seen, further suggesting the relevance of this experimental model. Thus, AIDS patients with cryptococcosis produce an immune response that reflects the dissemination but not the meningeal involvement. This murine model of disseminated cryptococcosis can be used to investigate the pathophysiology of cryptococcosis and new therapeutic approaches.

* Corresponding author. Mailing address: Unité de Mycologie, Institut Pasteur, 25, rue du Dr.-Roux, 75724 Paris Cedex 15, France. Phone: 33 1 40 61 33 89. Fax: 33 1 45 68 84 20. E-mail: dromer{at}pasteur.fr.

Infection and Immunity, December 1999, p. 6314-6320, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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