Abstract
Induction of IDO is also under strict control by the immune system and we have previously shown that there are a number of cytokines involved in the down-regulation of IDO induction. In clinical practice anti-inflammatory substances and antibiotics are commonly used and may influence the outcome of bacterial infection. We analysed the IFNy-dependant IDO induction and bacteriostasis ofStaphylococcus aureusand Group A Streptococcus (GAS) in monocyte-derived-macrophages (MDM) from cord blood and peripheral blood of healthy adult donors with attention to the effect of down-regulatory cytokines and of two commonly used anti-inflammatory agents, hydrocortisone and indomethacin, on both IDO activity and bacterial growth. In addition to this we were interested in the effect of sub-inhibitory concentrations of the antibiotic ampicillin on this IDO-mediated effect, the premise being that for a substantial period of antibiotic therapy the infection site is exposed to sub-inhibitory concentrations of antibiotic. We found that after stimulation with IFNy, MDM inhibited streptococcal growth. This was due to IFNy-induced IDO activity as demonstrated by reconstitution of growth by supplemental tryptophan. This IDO-mediated bacteriostasis was inhibited by the cytokines IL-10, IL-4 and TGF3. Furthermore, addition of indomethacin to IFNy stimulated MDM also resulted in the abrogation of the IDO-induced bacteriostasis, a result of the inhibition of IDO induction. Surprisingly, co-stimulation with hydrocortisone and IFNy apparently increased the IDO activity in cord blood MDM, but had no effect on the IDO-activity of adult peripheral blood MDM. Bacteriostasis in cord blood MDM, on the other hand, was not affected by co-stimulation with hydrocortisone. Ampicillin, in sub-inhibitory concentrations had no effect on the IDO activity itself but did have a synergistic effect on the IDO-induced bacteriostasis in MDM cultures
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MacKenzie, C.R., Worku, D., Däubener, W. (2003). Regulation of Ido-Mediated Bacteriostasis In Macrophages: Role of Antibiotics And Anti-Inflammatory Agents. In: Allegri, G., Costa, C.V.L., Ragazzi, E., Steinhart, H., Varesio, L. (eds) Developments in Tryptophan and Serotonin Metabolism. Advances in Experimental Medicine and Biology, vol 527. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0135-0_7
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DOI: https://doi.org/10.1007/978-1-4615-0135-0_7
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