IGF-I/IGFBP-3 Equilibrates Ratios of Pro- to Anti-inflammatory Cytokines, Which Are Predictors for Organ Function in Severely Burned Pediatric Patients
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BACKGROUND: We hypothesized that ratios of pro- to anti-inflammatory cytokines can be associated with hepatic, cardiac, and renal function after a severe trauma and can be used as predictors for clinical outcome. Furthermore, insulin-like growth factor-I (IGF-I) in combination with its principle binding protein (IGFBP-3) equilibrates pro- to anti-inflammatory cytokine ratios and improves homeostasis of severely burned pediatric patients. MATERIALS AND METHODS: Seventeen severely burned children were given a continuous infusion of IGF-I/BP-3 for 5 days after wound excision and grafting; seven were given saline during the same time period to serve as controls. Patient demographics and mortality were determined. Five days after excision and grafting, cardiac function was determined and blood samples were taken for serum levels of IGF-I, IGFBP-3, creatinine, pre-albumin, cholinesterase, pro-inflammatory cytokines (IL-1beta, IL-6, and TNF), and anti-inflammatory cytokines (IL-2, IL-4, IL-10 and IFN-gamma). RESULTS: There were no differences between IGF-I/BP-3 and controls in age, gender, burn size, or mortality. Serum IGF-I in burned children given the IGF-I/BP-3 complex increased from 102 + 15 to 433 + 33 microg/ml and IGFBP-3 increased from 1.5 + 0.2 to 3.0 + 0.2 microg/ml (p < 0.05). Serum pre-albumin and cholinesterase increased with IGF-I/BP-3, whereas serum creatinine decreased when compared to controls (p < 0.05). IGF-I/BP-3 increased cardiac index by 16% and stroke volume index by 15% (p < 0.05). These improvements in organ homeostasis were associated with decreased ratios of pro- to anti-inflammatory cytokines in the IGF-I/BP-3 group when compared to controls (p < 0.05). CONCLUSIONS: Increased ratios of pro- to anti-inflammatory cytokines may indicate a higher risk for the incidence of multi-organ failure. We therefore suggest that ratios of pro-inflammatory to anti-inflammatory cytokines can be used to predict organ function. We further conclude that IGF-I/BP-3 equilibrates the balance between pro- and anti-inflammatory cytokines, which was associated with improved cardiac, renal, and hepatic function. The benefit of IGF-I/BP-3 in ameliorating the inflammatory response may also apply in reducing the multi-organ failure often observed in the state of severe trauma.
