EFFECT OF CYTOKINES ON HUMAN NEUTROPHIL FUNGICIDAL AND FUNGISTATIC ACTIVITIES AGAINST Paracoccidioides brasiliensis

THESIS.D. R. Domingues submitted this dissertation for her Masters in Tropical Diseases at Botucatu School of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil, 2003.

Advisor: Professor Ângela M. V. Campos Soares.

ABSTRACT. Human polymorphonuclear leukocytes (PMNs) fungicidal and fungistatic activities against high virulent Paracoccidioides brasiliensis strain were studied. These effects were tested in short-term (4h) and long-term (24h and 48h) cocultures. Non-activated PMNs failed to exhibit antifungal activity in all studied periods. However, IFN-g-activated cells showed fungicidal activity in short-term cocultures (4h). No fungistatic and fungicidal activities were detected in long-term cocultures (24h and 48h). TNF-a-activated PMNs showed fungicidal activity in short and long-term cocultures (4h and 24h), while GM-CSF stimulated PMNs both for fungicidal and fungistatic activities in short and long-term cocultures (4, 24, and 48 hours). IFN-g and TNF-a antifungal effects were inhibited or abrogated when P. brasiliensis occurred in the presence of catalase (CAT) and superoxide dismutase (SOD), showing the role of H₂O₂ and superoxide anion in antifungal activity. For GM-CSF-activated cells, superoxide anion was the main involved metabolite. Based on these data, PMN cell role in early and late P. brasiliensis stages is discussed.

KEYWORDS: Paracoccidioides brasiliensis; Human neutrophils; Interferon-gamma (IFN-g); Tumor necrosis factor alpha (TNF-a); Granulocyte macrophage colony stimulating factor (GM-CSF).

CORRESPONDENCE TO: Daniela Ramos Rodrigues – Rua General Glicério, 1001, 08674-003, Suzano, São Paulo, Brasil, Phone:  55 11 47488742 – E-mail: rodriguesdn@yahoo.com.br