has been reported for patients undergoing DFO therapy ( 13, 15, 40). Moreover, fatal septicemia with Yersinia and other microorganisms including the fungus Rhizopus sp. enterocolitica in mice, resulting in fatal septicemia and shock ( 5, 39, 40). In keeping with these observations, we and others have demonstrated that DFO increases pathogenicity of Y. DFO inhibits proliferation of T and B lymphocytes and cytokine production of macrophages and modulates interaction of polymorphonuclear leukocytes with yersiniae ( 3, 21). On the other hand, DFO exerts effects on various components of the immune system of the host. The genes encoding FO uptake have been characterized and are considered part of the virulence factors required for high-level pathogenicity of Yersinia ( 10, 11). In fact, iron-loaded DFO (ferrioxamine ) can be taken up and used as an iron source by Yersinia ( 16, 36). enterocolitica by iron provision to the pathogen and immunosuppression of the host. Previous work from this laboratory showed that desferrioxamine (DFO) may play a dual role in pathogenesis of Yersinia infection: growth and virulence promotion of Y. In immunocompromised patients or patients with iron overload, Yersinia causes systemic infections with abscesses in spleen and liver ( 27, 33, 37). Infection with this pathogen causes a wide range of clinical manifestations including enterocolitis and mesenteric lymphadenitis ( 28). Yersinia enterocolitica is a gram-negative bacterium which is pathogenic for humans and rodents ( 23, 25). These results strongly suggest that HES-DFO might be a favorable drug with fewer side effects than DFO in terms of DFO-promoted fulminant infections. Moreover, our data suggest that DFO needs to be taken up by host cells in order to exert its immunosuppressive action. Thus, due to the delayed in vivo effect HES-DFO failed to trigger Yersinia-induced septic shock, which accounts for early mortality in DFO-associated septicemia. However, some of the HES-DFO-treated mice died 8 to 14 days postinfection. enterocolitica, while none of the mice pretreated with HES-DFO died within the first 7 days postinfection. The pretreatment of mice with DFO resulted in death of all mice 2 to 5 days after application of a normally sublethal inoculum of Y. enterocolitica possibly due to cleavage of HES and release of DFO. Nevertheless, in vivo HES-DFO promoted growth of Y. ![]() We found HES-DFO to promote neither growth of Yersinia enterocolitica nor mitogen-induced T-cell proliferation and gamma interferon production by T cells in vitro. In this study, we sought to determine whether conjugation of DFO to hydroxyethyl starch (HES-DFO) may prevent exacerbation of Yersinia infection in mice. Previous work from our laboratory showed that this might be due to a dual role of DFO: growth promotion of the pathogen and immunosuppression of the host. As a side effect, DFO may favor the occurrence of fulminant Yersinia infections. The iron chelator desferrioxamine (DFO) B is widely used in the therapy of patients with iron overload.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |