Cytokine, infiltrating macrophage and T cell-mediated response to development of primary and secondary human liver cancer

Abstract Background . Kupffer cells, monocytes and infiltrating T cells have been considered the major source of interleukin-1β and tumour necrosis factor-alpha in the liver. Aims . To explore the expression of interleukin-1β and tumour necrosis factor-alpha and to evaluate the density and the distribution of T lymphocytes and monocytes/macrophages in the liver of patients with primary and secondary tumours. Methods . Tumoural and peritumoural liver samples were examined from 21 patients with hepatocellular carcinoma, 1 D with hepatic metastases, 5 with benign focal liver lesions and 4 healthy adult livers. Interleukin-1β and tumour necrosis factor-alpha mPNAs were detected by a semiquantitative comparative reverse transcriptase polymerase chain reaction. T lymphocytes and monocytes/macrophages were detected by immunohistochemistry Results . Higher levels of interleukin-1β, tumour necrosis factor-alpha, CD3+ and CD68+ cells were found in the tissue surrounding hepato-cellular carcinoma and metastases than in the tumour itself. A strong expression of CD68+ and CD3+ cells was found mainly along the tumour-host interface but the highest expression of CD3+ cells was found at the metastasis interfaces. Interleukin-1β expression, CD3+ and CD68+ cell densities were higher in peritumoural samples than in so-called “normal” liver tissue. Conclusions . An increased production of interleukin-1β and, to a lesser extent, of tumour necrosis factor-alpha mRNA coincides with the presence of cancer, be it primary or secondary, both in healthy and cirrhotic livers. The presence of cancer, irrespective of the presence of underlying liver damage, appears to play the most important role.