CELLULAR-LOCALIZATIONS OF INTERLEUKIN-1-BETA, INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RNA IN A PARASITIC GRANULOMATOUS-DISEASE OF THE LIVER, ALVEOLAR ECHINOCOCCOSIS

Alveolar echinococcosis (AE), an uncommon and very severe parasitic li ver disease, can be considered as an ''infectious model'' of granuloma tous disease, where cellular immunity plays a key role in the defence against Echinococcus multilocularis, the larval cestode responsible fo r the disease. We analysed the localisation of the expression of the p ro-inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha mRNA in human AE liver lesions, in the periparasitic granulomas and in the hepatic p arenchyma, as well as the phenotypic characteristics of the cells on s erial sections. In situ hybridizations, using anti-sense S-35 dUTP-lab eled IL-1 beta, IL-6 and TNF-alpha riboprobes, were performed on cryos tat liver sections; the sense probes were used as negative controls. I L-1 beta, IL-6 and TNF-alpha mRNA were observed in macrophages located at the extreme periphery of the granuloma, between the lymphocytic ri ng and the liver parenchyma, in patients with active AE. No cytokine m RNA expression was observed in a patient with an abortive case. Only T NF-alpha mRNA was located in the periparasitic area, in cells morpholo gically identified as macrophages but exhibiting an unusual phenotype (CD 11(b)(-), CD 25(+)); this particular expression was observed only in those patients with very fertile lesions, associated with centro-gr anulomatous necrosis. These results show that pro-inflammatory cytokin es are consistently produced by macrophages at the periphery of the pe riparasitic granuloma and can serve as mediators of acute-phase protei n secretion and of fibrogenesis in that location. Presence of isolated cytokine mRNA expressing cells in the liver lobules and portal tracts could explain the spread of the fibrous process to the whole liver. T NF-alpha MRNA expression by cells in contact with the larvae in some p atients, dealing to necrosis, could be a new example of how parasites use immune responses for their own survival and growth.