Differential expression of suppressors of cytokine signalling genes in response to nutrition and growth hormone in the septic rat

GH treatment during critical illness and sepsis may increase mortality. A f maily of negative regulators of cytokine signalling, the suppressors of cyt okine signalling (SOCS), have been characterised. SOCS provide a mechanism for cross-talk between the cytokine receptors, including GH. Here, we have investigated the impact of nutrition and GH treatment on GH receptor, SOCS- 1, SOCS-2, SOCS-3 and cytokine-inducible SH2-containing protein (CIS) hepat ic mRNA expression in a rat model of sepsis, caecal ligation and puncture ( CLP). Four groups of rats were studied: control (food given ad libitum, n=7), CLP only (n=8), CLP and total parenteral nutrition (TPN) (n=9), and CLP, TPN a nd GH (n=10). CLP rats underwent surgery and 18 h later received saline or TPN or TPN+GH for G h before they were killed. Serum IGF-I levels were lower in all CLP groups (P <0.001). The combination of TPN and GH treatment increased IGF-I levels compared with the saline-tr eated CLP rats (P <0.01), but IGF-I levels remained lower than control anim als (P <0.001). GH receptor and GH-binding protein expression in liver was reduced in animals subjected to CLP and was unaffected by nutrition or GH t reatment. Hepatic SOCS-1 was detectable in normal rats, induced in all CLP animals but was unaffected by nutrition and GH. Hepatic SOCS-2 expression w as difficult to detect in normal and CLP rats but was greatly induced in CL P rats treated with GH. Hepatic SOCS-3 expression was only just detectable in the control group but was elevated in all CLP groups and unaffected by n utrition and GH. Hepatic CIS expression was difficult to detect in normal r ats, was not induced by CLP but was induced by both nutrition and GH. In conclusion. CLP induced low IGF-I levels associated with increased expre ssion of SOCS-1 and SOCS-3, both of which are known to inhibit GH receptor signalling. GH induced SOCS-2 and CIS in the CLP rat despite resistance wit h respect to IGF-I generation, and parenteral feeding induced CIS in the CL P rat. Thus. there is potential for a complex interaction between GH and cy tokine signalling at the level of SOCS expression whereby the inflammatory response may alter GH signalling and GH may influence the inflammatory resp onse.