P006 Cytokine and chemokine responses as predictive markers for progressive, stable or cured Echinococcus multilocularis infection in man

Abstract

Introduction In man the tissue infiltrative growth of Echinococcus multilocularis metacestodes will cause alveolar echinococcosis (AE) with organ malfunction and finally organ failure. In some AE patients, however, metacestode proliferation may regress, but little is known about the mechanism and determinants which may control or even restrain parasite survival and its growth. Methods In this study, chemokine and cytokine responses were investigated in E. multilocularis patients at different states of infection, i.e. with progressive, stable and cured alveolar echinococcosis. We analyzed the serum levels and the ex vivo cytokine and chemokine responsiveness of peripheral blood mononuclear cells (PBMC) from AE patients, reflecting their innate and memory immune responses to E. multilocularis antigens. First, plasma concentrations of pro-inflammatory cytokines and chemokine were investigated, and then the capacity of PBMC from AE patients and infection-free controls was studied in order to distinguish between progressive, stable and cured E. multilocularis infection. Results The plasma levels of the pro-inflammatory cytokines IL-17B and its soluble receptor (sIL-17RB), and MIP-3 α were highly elevated in AE patients as compared to controls while highest concentrations of IL-17F and its common soluble receptor (sIL-17RA), regulatory IL 27, pro-inflammatory IL 31 and IL 33 were detected in controls. Spontaneous release of several cytokines and chemokine was clearly different between AE patients in different stages of infection and controls. Furthermore, a distinct cellular responsiveness was observed in AE patients when their PBMC were activated with antigens from helminthes, bacteria or mitogens. Pro-inflammatory cytokine production of IL17F and IL 17RA, as well as regulatory IL27, was reduced above baseline level in AE patients when their PBMC were co-culture with Em Antigens. Chemokine production of PBMC in AE patients was not inducible by E.multilocularis antigens for pro-inflammatory monocyte inflammatory proteins (MIP-1 α /CCL3//MIP-1 β /CCL4//MIP-3 α /CCL20). Conclusion These observations disclose a distant dynamic of the cytokine and chemokine profile at different stages of AE. Furthermore, cestode and nematode antigens will differ in their capacity to stimulate cellular cytokine and chemokine production, notably for the activation of pro-inflammatory immune mediators. In summary, the analyses of constitutive and inducible chemokine and cytokine profiles may provide a better understanding of their importance during progression, regression and also for the staging of alveolar echinococcosis.