Cellular localisations of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha mRNA in a parasitic granulomatous disease of the liver, alveolar echinococcosis.

Alveolar echinococcosis (AE), an uncommon and very severe parasitic liver disease, can be considered as an "infectious model" of granulomatous disease, where cellular immunity plays a key role in the defence against Echinococcus multilocularis, the larval cestode responsible for the disease. We analysed the localisation of the expression of the pro-inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha mRNA in human AE liver lesions, in the periparasitic granulomas and in the hepatic parenchyma, as well as the phenotypic characteristics of the cells on serial sections. In situ hybridizations, using anti-sense 35S dUTP-labeled IL-1 beta, IL-6 and TNF-alpha riboprobes, were performed on cryostat liver sections; the sense probes were used as negative controls. IL-1 beta, IL-6 and TNF-alpha mRNA were observed in macrophages located at the extreme periphery of the granuloma, between the lymphocytic ring and the liver parenchyma, in patients with active AE. No cytokine mRNA expression was observed in a patient with an abortive case. Only TNF-alpha mRNA was located in the periparasitic area, in cells morphologically identified as macrophages but exhibiting an unusual phenotype (CD 11b-, CD 25+); this particular expression was observed only in those patients with very fertile lesions, associated with centro-granulomatous necrosis. These results show that pro-inflammatory cytokines are consistently produced by macrophages at the periphery of the periparasitic granuloma and can serve as mediators of acute-phase protein secretion and of fibrogenesis in that location.(ABSTRACT TRUNCATED AT 250 WORDS)