Enzymatically inactive eosinophil peroxidase inhibits proinflammatory cytokine transcription and secretion by macrophages.

The present investigators have reported previously that macrophages (Mphi) can bind either myeloperoxidase (MPO) or eosinophil peroxidase (EPO) resulting in enhanced cytotoxicity to Candida albicans. Since MPO was shown to be immunomodulatory, the present study was initiated to determine whether either EPO or partially fragmented EPO (fgEPO) also modulated cytokine secretion. Murine peritoneal Mφ simultaneously stimulated with fgEPO and one of the following, (1) LPS, (2) mannosylated bovine serum albumin (mBSA), (3) interferon-gamma (IFN-gamma), or (4) Poly I:C, demonstrated both dose- and time-dependent decreases in TNF-alpha and IL-6 and a dose-dependent decrease in IFN-alpha/beta. The mRNA levels of Mphi exposed to fgEPO and mBSA demonstrated that fgEPO modulated Mphi cytokine function by decreasing TNF-alpha and IL-6 mRNA transcripts without altering transcription of TGF-beta or GM-CSF. These results demonstrate a possible interaction between the Mphi and eosinophil that could result in reduction of inflammation.