Inflammatory cytokines and acquired growth hormone resistance

Resistance to growth hormone (GH)-mediated induction of insulin-like growth factor I (IGF-I) is a common complication of catabolic diseases, including critical illness and post-surgical conditions. This resistance to GH is be lieved to be permissive to the development of protein catabolism, cachexia and wasting, which are associated with an increased mortality rate. Data fr om in vitro studies and animal models suggest that increased levels of infl ammatory cytokines can induce cachexia and might inhibit the effects of GH on target tissues. The molecular mechanisms involved are unclear, although an effect of cytokines on GH receptor signalling has been suggested. The GH -activated pathways that mediate the increase in IGF-I levels are not well understood, thereby impeding the elucidation of the effect of inflammatory cytokines. Several signalling cascades, like the JAK-STAT and MAP kinase pa thways, have been shown to be activated by GH and some inflammatory cytokin es, hence raising the possibility of crosstalk on this level. Our data, how ever, indicate that inflammatory cytokines have little or no effect on GH-m ediated JAK-STAT signalling. In this review, we discuss these results and t he possibility that secondary changes in the structure of chromatin are lik ely to be involved in the induction of IGF-I gene transcription by GH. (C) 2000 Harcourt Publishers Ltd.