Invasive aspergillosis is a serious complication in immunocompromised patients. The effects of recombinant human tumor necrosis factor alpha (TNF-α) on antifungal activities of human neutrophils (polymorphonuclear leukocytes [PMNs]), human monocytes (MNCs), and rabbit pulmonary alveolar macrophages (PAMs) againstAspergillus fumigatus were studied. The percentage of PMN-induced hyphal damage was increased after 30 min of incubation of PMNs with 0.1 ng of TNF-α per ml at 37°C (P = 0.043). At 0.1 to 10 ng/ml, TNF-α also increased superoxide anion (O2 −) produced by PMNs in response to phorbol myristate acetate, N-formylmethionyl leucyl phenylalanine, and unopsonized hyphae (P < 0.01) but did not exert any effect on PMN phagocytosis of conidia in the presence of serum. By comparison, TNF-α induced only a slight increase in O2 − production by MNCs in response to phorbol myristate acetate (P = 0.05) and no concomitant increase in the percentage of MNC-induced hyphal damage. Incubation of MNCs with TNF-α at 0.001 to 10 ng/ml for 2 days had no effect on phagocytosis or conidiocidal activity. By contrast, incubation of PAMs with TNF-α at 0.1 to 10 ng/ml for 2 days increased phagocytosis of conidia (P = 0.03). Thus, TNF-α augments the capacity of PMNs to damage Aspergillus hyphae, possibly through enhanced oxidative mechanisms, and increases PAM phagocytic activity against conidia. As such, TNF-α may have an important role in host defense against aspergillosis, and neutralization of its activity may be complicated by increased susceptibility to aspergillosis.

OBJECTIVE: To analyze invasive Candida infections in pediatric patients and to examine the outcome of disease. METHODS: An observational prospective study was carried out of microbiologically documented cases of invasive candidosis in neonates, infants and children at Hippokration Hospital from December 1993 to July 1995. RESULTS: Thirty-nine cases of invasive candidosis (mainly candidemia and candiduria) occurred in 38 patients aged 3 days to 14 years, 21 (54%) having occurred in patients aged <1 month. The incidence was 10.1/1000 admissions in the two neonatal departments versus 1.1/1000 for all other pediatric departments, including oncology (p<0.01). The most frequent causes of hospitalization were premature birth or perinatal problems and surgery. Thirty-five strains of Candida albicans, 10 of C. parapsilosis and eight of other or unidentified species were isolated. Non-C. albicans isolates, especially C. parapsilosis and C. glabrata, exhibited higher minimal inhibitory concentrations of azoles as compared with C. albicans. Thirteen patients (34%), all candidemic, died within 0--40 days. Untreated patients more frequently had positive cultures up to time of death (p<0.0001) and died (p=0.0006). CONCLUSIONS: Invasive candidosis is frequent in pediatric patients, especially premature neonates, and is associated with increased mortality. With early diagnosis and initiation of therapy the outcome is favorable.

The effects of interleukin (IL)-10, a potent antiinflammatory cytokine, on human monocyte functions against two medically important pathogens, Candida albicans and Staphylococcus aureus, were studied. Incubation with 20-100 ng/mL IL-10 for 2-3 days decreased the fungicidal activity of monocytes against serum-opsonized C. albicans blastoconidia (P

The potential of recombinant human interleukin-12 (IL-12) to enhance the capacity of human monocytes (MNC) to elicit an oxidative burst and damage hyphae of Aspergillus fumigatus was investigated. Incubation of peripheral blood mononuclear cells (PBMC) from healthy adults with 10 to 100 ng of IL-12/ml at 37°C for 2 to 3 days enhanced the production of superoxide anion (O2 −) in response to phorbol myristate acetate (PMA) (P = 0.04) and unopsonized A. fumigatus hyphae (P = 0.03) and further enhanced hyphal damage (P = 0.009). Anti-gamma interferon (anti-IFN-γ) blocked secretion of IFN-γ by IL-12-treated PBMC but did not inhibit IL-12-induced O2 − production by these cells in response to PMA. In addition, IL-12-treated elutriated MNC secreted no IFN-γ or tumor necrosis factor alpha but exhibited enhanced O2 − production compared to controls (P = 0.013). These findings demonstrate that IL-12 augments oxidative antifungal activities of MNC via an IFN-γ-independent route, suggesting a novel pathway of IL-12 action in antifungal defense.