Cytokines comprise a group of small proteins released from cells in order to influence the function of other cells. By binding to highly specific cell-surface receptors, they trigger a vast array of intracellular signalling cascades. Cytokines have been described as interleukins, growth factors, interferons and chemokines. Unlike hormones, which act in a similar way, cytokines are produced by many different types of cell and act on many other types. Most of them are produced only after certain stimuli. The most intense field of cytokine activity is without doubt host defence. The liver resembles a central organ of cytokine activity due to the fact that it hosts hepatocytes, which are highly susceptible to the activity of cytokines in a variety of physiological and pathophysiological processes. Moreover, the non-parenchymal cells of the liver, in particular Kupffer cells (KCs), the resident tissue macrophages of the liver, are able to synthesize a variety of cytokines that may act systemically on any other organ of the body, or in a paracrine manner on hepatocytes and other non-parenchymal liver cells. A classic example of how cytokines act can be observed during the acute phase reaction discussed in this article. The role of cytokines in liver development, acute liver injury, liver regeneration, liver fibrosis and liver metastasis is also discussed.

To model the cytogenetic evolution in gastrointestinal stromal tumour (GIST), an oncogenetic tree model was reconstructed using comparative genomic hybridization data from 203 primary GISTs (116 gastric and 87 intestinal GISTs, including 151 newly analysed cases), with follow-up available in 173 cases (mean 40 months; maximum 133 months). The oncogenetic tree model identified three major cytogenetic pathways: one initiated by -14q, one by -1p, and another by -22q. The -14q pathway mainly characterized gastric tumours with predominantly stable karyotypes and more favourable clinical course. On the other hand, the -1p pathway was more characteristic of intestinal GISTs, with an increased capacity for cytogenetic complexity and more aggressive clinical course. Loss of 22q, more closely associated with -1p than -14q, appeared to initiate the critical transition to an unfavourable cytogenetic subpathway. This -22q pathway included accumulation of +8q, -9p, and -9q, which could all predict disease-free survival in addition to tumour site. Thus, insights into the cytogenetic evolution obtained from oncogenetic tree models may eventually help to gain a better understanding of the heterogeneous site-dependent biological behaviour of GISTs.

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