Effects of granulocyte and granulocyte-macrophage colony-stimulating factors in a neutropenic murine model of trichosporonosis

Abstract

We produced disseminated trichosporonosis in a neutropenic murine model with Trichosporon asahii, which was identified by DNA relatedness analysis. We then assessed the efficacy of granulocyte colony-stimulating factor (G-CSF) (30 to 100 g/kg of body weight per day) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.8 to 2 g/kg ⅐ day). The administration of G-CSF either before or after infection improved 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 alpha (TNF-␣) in bronchoalveolar lavage fluid (BALF) of neutropenic and G-CSF-pretreated mice were 60 ؎ 6 ng/ml and 18 ؎ 6 pg/ml, respectively, at 24 h after infection. Immunohistologically, alveolar macrophages proved to be the main source of TNF-␣ in BALF. GM-CSF increased neutrophil counts less significantly than did G-CSF and increased the lethality (P < 0.05) with a high level of TNF-␣ in BALF. Expecting to inhibit TNF-␣, we administered anti-TNF-␣ intraperitoneally at the dose completely inhibiting TNF-␣ in plasma (2 ؋ 10 4 U), but the TNF-␣ level in BALF and the lethality increased. Though 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-␣ overproduction in the lungs, have an important role in the prognosis of trichosporonosis.

Cytokines and fungal infections

“…Furthermore, ex vivo incubation with G-CSF enhanced the impaired respiratory burst of neutrophils derived from transplant recipients against Candida and Cryptococcus yeasts as well as Aspergillus and Rhizopus conidia (Pursell et al, 2003). Treatment with G-CSF in neutropenic animal models of invasive candidiasis, aspergillosis or trichosporonosis was associated with faster recovery from neutropenia and improved survival (Hamood et al, 1994;Muranaka et al, 1997;Graybill et al, 1998). Recent studies, however, have demonstrated an additional important role of G-CSF in the regulation of adaptive T helper-cell responses.…”

In vivo lipid‐derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS

“…As described previously (25), three injections and aspirations with 10 mL of sterile ice-cold saline containing 1 mM EDTA were used to collect the BAL fluid in the rat. Cells from BAL fluid were determined by using a hemocytometer and differential cell counts were performed on 500 cells from BAL fluid with a modified Wright's stain.…”

Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes againstTrichosporon asahii

“…While TNF-a may enhance the host defence mechanisms against the invading microorganisms, previous studies have shown that large amounts of TNF-a released during the acute stages of infection may actually worsen the condition. In this regard, Muranaka et al [26] suggested that TNF-a overproduction in the lung has an important role in the prognosis of trichosporonosis. The peak concentrations of TNF-a in the plasma and bronchoalveolar lavage¯uid in their model at 24 h after infection were 742 6 104 pg/ml and 60´1 6 6´3 ng/ml, respectively.…”