Production of Tumor Necrosis Factor-α in Granulocytopenic Mice with Pulmonary Candidiasis and Its Modification with Granulocyte Colony-Stimulating Factor

  • FUTENMA Mitsuhiko
    First Department of Internal Medicine, Faculty of Medicine, University of Ryukyus
  • KAWAKAMI Kazuyoshi
    First Department of Internal Medicine, Faculty of Medicine, University of Ryukyus
  • SAITO Atsushi
    First Department of Internal Medicine, Faculty of Medicine, University of Ryukyus

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In the present study, a lethal model of pulmonary candidiasis was established using granulocytopenic mice with cyclophosphamide. These mice started to die 1 day after infection and had all died within the next 48hr. The counts of live C. albicans in the lung gradually increased with time, while the organisms were quickly eliminated in the normal mice. From the histology and measurements on bronchoalveolar lavage fluid (BALF), polymorphonuclear cells (PMN) response was almost zero up to 24hr, and then a weak but significant response was observed at 48hr, while a marked accumulation of PMN was detected from as early as 6hr in normal mice. In contrast, macrophages had accumulated in BALF by 48hr in granulocytopenic mice, but not in normal mice. Both in serum and BALF, a considerable level of tumor necrosis factor-α (TNF-α) was detected from 6hr, peaking at 24 to 48hr, while in normal mice the quantity was under the detection limit in serum and very low in BALF. The effects of administering granulocyte colony-stimulating factor (G-CSF) on these parameters were next examined. G-CSF significantly prolonged the survival time of granulocytopenic mice, promoted the clearance of organisms through increasing the counts of PMN in the lung, and strongly inhibited the production of TNF-α both in BALF and serum. These results suggest that this cytokine does not protect them, but plays some role in their death due to candidial infection in granulocytopenic mice.

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