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 believed to be permissive to the development of
protein catabolism,
cachexia and wasting, which are associated with an increased mortality rate. Data from in vitro studies and animal models suggest that increased levels of inflammatory
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 pathways, have been shown to be activated by GH and some inflammatory
cytokines, hence raising the possibility of crosstalk on this level. Our data, however, indicate that inflammatory
cytokines have little or no effect on GH-mediated JAK-STAT signalling. In this review, we discuss these results and the possibility that secondary changes in the structure of
chromatin are likely to be involved in the induction of
IGF-I gene transcription by GH.