Experimental paracoccidioidomycosis of the Syrian hamster: fungicidal activity and production of inflammatory cytokines by macrophages

Phagocytic cells play an important role in nonspecific resistance to fungal infection by mediating an inflammatory response and by a direct fungicidal action. In this study, the functional activity of peritoneal macrophages o btained from hamsters experimentally infected with strain Pb18 of Paracocci dioides brasiliensis was evaluated during 16 weeks of infection. The result s showed that macrophages had a higher spreading ability associated with in creased production of tumor necrosis factor alpha (TNF-alpha) and enhanced fungicidal activity during the early periods of infection. TNF-alpha levels remained elevated during all periods studied, while low levels of interleu kin-1 beta (IL-1 beta) were produced during the infection. A necrotic area with dead fungi was observed at the inoculation site and the infection diss eminated only to liver and lymph nodes in a few animals. These results sugg est that during the early stages of infection with P. brasiliensis, macroph age activation by the high levels of TNF-alpha limited fungal dissemination . In contrast, in the later stages of infection, high levels of TNF-alpha w ere observed while the fungicidal activity of macrophages was lower and the animals presented loss of vitality resulting in their death. These observa tions suggest a complex role of TNF-alpha in experimental paracoccidioidomy cosis of Syrian hamsters, involving not only resistance but also pathogenes is.