Summary:diagnostic procedures further decrease the natural resistance to infection. Finally, granulocytopenia compromises the first line of defense against bacterial, fungal and paraType, severity and incidence of infection during the neutropenic period after peripheral blood stem cell transsitic pathogens. Fever of unknown origin, bacteremia and pneumonia are the most frequent clinical manifestations of plantation (PBSCT) for treatment of malignant disease were studied in 66 patients treated at a single instiinfection in patients after chemotherapy. 3 Infections with both gram-positive and gram-negative bacteria as well as tution. Data of 34 female and 32 male patients with a median age of 43 years suffering from leukemia (12), fungi are common in these patients. In particular, staphylococci, streptococci, E.coli, klebsiella, pseudomonas, canlymphoma (35), multiple myeloma (six) or solid tumors (13) were retrospectively analyzed. All patients had dida and aspergillus species are frequently isolated from infectious sites in granulocytopenic patients. received at least 2.5 ؋ 10 6 CD34-positive cells for stem cell rescue after high-dose chemotherapy. Ninety-fourChemotherapeutic agents display a dose-response relationship in vivo and in vitro. 4,5 However, the application percent of the patients experienced at least one febrile episode during their post-transplant course. The of high-dose chemotherapy is limited by its toxic effects, in particular on the hematopoietic system. Stem cell rescue patients recovered quickly and defervesced after a median of 4 days. The incidence of bacteremia was 39%by autologous bone marrow transplantation has been applied to circumvent the dose-limiting hematopoietic toxand gram-positive cocci were the predominant pathogens. In contrast, severe organ infections were rare.icities. 6-8 Myeloablative therapies with autologous bone marrow transplantation, however, cause prolonged marrow Only 5% of the patients suffered from lung infiltrates. No invasive fungal infections were observed. No transaplasia accompanied by severe infectious complications. Autologous bone marrow transplantation caused a transplant-related deaths occurred in the 66 patients studied. We conclude that the severe, but shortlasting neutroplant-related mortality consistently in the range of 5-10%. 6-8 Mobilization of peripheral hematopoietic stem penia after peripheral blood stem cell transplantation is associated with a high incidence of bacterial infection.cells by chemotherapy and growth factors and leukapheresis yields higher numbers of hematopoietic stem cells than The severity of the majority of these infections is moderate. With appropriate anti-infective therapies these bone marrow harvesting. 9,10 Numerous reports have meanwhile confirmed the feasibility and effectiveness of transinfections can be managed and life-threatening infectious complications, in particular fungal infections, are plantation with peripheral blood stem cells (PBSCT) to mitigate the hematotoxic effects of myeloablative therrare. Empiric...
In the present study, we investigated the effect of interferon-alpha (IFN-alpha) on the expression of interleukin-10 (IL-10) mRNA and protein synthesis in human monocytes and CD4+ T cells. In mononuclear cells, IFN-alpha induced expression of IL-10 mRNA and further enhanced lipopolysaccharide (LPS)-stimulated IL-10 expression. In purified monocytes, a strong expression of IL-10 mRNA induced by LPS was not further enhanced by IFN-alpha. In highly purified CD4+ T cells, IFN- alpha upregulated IL-10 mRNA upon activation with phytohemagglutinin and phorbol myristate acetate. In purified monocytes, an effect of IFN- alpha on IL-10 protein synthesis was dependent on costimulation with LPS. Maximal stimulation of IL-10 protein by IFN-alpha was seen after prolonged incubation periods of 48 to 96 hours, whereas IFN-gamma reduced IL-10 production in the early incubation period. Similar effects of IFN-alpha were observed in CD4+ T cells activated with CD3 and CD28 monoclonal antibodies. Addition of IFN-alpha caused an increase of IL-10 in culture supernatants of activated T-helper cells of more than 100% after 96 hours of incubation. In contrast, other cytokines, including IFN-gamma and IL-4, had no influence on IL-10 secretion stimulated by CD3 and CD28 in CD4+ T cells. In serum samples of IFN-alpha-treated individuals, we failed to detect an influence of cytokine treatment on IL-10 serum levels, confirming the requirement of additional activating signals for IFN-alpha-mediated effects on IL-10 synthesis. In conclusion, IFN-alpha enhances the late induction of IL- 10, which physiologically occurs upon stimulation of monocytes and T cells. Biologically, this effect might enhance the negative-feedback mechanism ascribed to IL-10, which limits inflammatory reactions.
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