Deferoxamine B but Not Deferoxamine G1 Inhibits Cytokine Production in Murine Bone Marrow Macrophages

Abstract

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 Band 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)-α mRNA production 4-fold (shown by semiquantitative reverse transcription polymerase chain reaction). TNF-α 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.