DEFEROXAMINE-B BUT NOT DEFEROXAMINE G1 INHIBITS CYTOKINE PRODUCTION IN MURINE BONE-MARROW MACROPHAGES

The iron chelator deferoxamine (DFO) B enhances virulence of Yersinia enterocolitica and modulates cellular immune responses. Since cytokines mediate effector mechanisms in resolution of yersiniae from infected tissues, the impact of DFO B and DFO G1 on cytokine production by murine bone marrow macrophages (BMM) was investigated. BMM were stimulated with lipopolysaccharide (LPS) of Salmonella typhimurium or infected with Y. enterocolitica. DFO B inhibited interleukin (IL)-6, IL-12, and tumor necrosis factor (TNF)-alpha mRNA production 4-fold (shown by semiquantitative reverse transcription polymerase chain reaction). TNF-alpha and IL-6 protein production was reduced 50% by DFO B. In contrast, DFO G1 had no effect on cytokine production. Moreover, cytokine production by Yersinia-infected BMM was decreased by plasmid-encoded Yersinia proteins. Thus, plasmid-cured strains induced higher cytokine responses in BMM than did the wild type strain. These results suggest that DFO B acts in a bimodal fashion in yersiniosis: iron supply to the pathogen and immunosuppression of the host.