EFFECTS OF GRANULOCYTE AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTORS IN A NEUTROPENIC MURINE MODEL OF TRICHOSPORONOSIS

We produced disseminated trichosporonosis in a neutropenic murine mode l with Trichosporon asahii, which was identified by DNA relatedness an alysis. We then assessed the efficacy of granulocyte colony-stimulatin g factor (G-CSF) (30 to 100 mu g/kg of body weight per day) and granul ocyte-macrophage colony-stimulating factor (GM-CSF) (0.8 to 2 mu g/kg. day). The administration of G-CSF either before or after infection imp roved the survival rate from less than 25% up to 100% (P < 0.05). The effects of G-CSF on organ clearance and histological examinations were most remarkable in the lungs. The levels of tumor necrosis factor alp ha (TNF-alpha) in bronchoalveolar lavage fluid (BALE) of neutropenic a nd G-CSF-pretreated mice were 60 +/- 6 ng/ml and 18 +/- 6 pg/ml, respe ctively, at 24 h after infection. Immunohistologically, alveolar macro phages proved to be the main source of TNF-alpha in BALF. GM-CSF incre ased neutrophil counts less significantly than did G-CSF and increased the lethality (P < 0.05) with a high level of TNF-alpha in BALF. Expe cting to inhibit TNF-alpha, we administered anti-TNF-alpha intraperito neally at the dose completely inhibiting TNF-alpha in plasma (2 x 10(4 ) U), but the TNF-alpha level in BALF and the lethality increased. Tho ugh the number of neutrophils at the early stage of infection appeared to be the most critical, the results suggest that other host defense mechanisms, such as TNF-alpha overproduction in the lungs, have an imp ortant role in the prognosis of trichosporonosis.