Objective: Hypercatabolism and immune dysfunction are closely associated with the development of systemic inflammatory response--multiple organ dysfunction (SIRS/MODS) in critical illness. It remains unclear however, whether leptin, an adipocyte-derived hormone whose levels are influenced by several cytokines and which regulates immune function, food-intake and energy expenditure is independently related to the development of and/or severity and mortality from SIRS/MODS.
Design and patients: To assess the role of leptin in SIRS/MODS we performed a matched case control and a longitudinal study (14 days) in 35 critically ill patients with SIRS/MODS and 35 matched controls.
Results: Baseline leptin levels were positively associated with body mass index (BMI) and TNF-alpha (P < 0.01) in patients and with IGF-1 and IL-6 levels (P < 0.05) in controls. Furthermore, leptin levels exhibited a progressive increase from the first to the last day of the study and although baseline levels were not different, peak leptin levels as well as leptin levels on the last day of the study were significantly higher in cases than in controls (P < 0.05). TNF-alpha levels, IL-6 and cortisol levels were also higher, whereas IGF-1 levels were lower in cases (P < 0.05). To assess whether leptin levels are independently associated with SIRS/MODS we performed multivariate logistic regression analysis which revealed that leptin up-regulation in cases is mediated by elevated TNF-alpha and cortisol levels. Finally, there was no independent association between leptin and survival in this group of critically ill patients.
Conclusion: We conclude that cytokines and cortisol upregulate leptin levels, which may contribute to the development of the hypercatabolism, wasting and immune dysfunction but leptin levels are not independently associated with severity or mortality of patients with systemic inflammatory response-multiple organ dysfunction.