Cytokine-driven inflammatory response is associated with the hypermetabolism of AIDS patients with opportunistic infections

Background: To assess a possible role of systemic inflammation in the resting metabolic response in AIDS patients with active secondary infections. Methods: Fifty-two patients with AIDS-defined criteria and concomitant active infections and 19 healthy subjects were studied. Measurements were as follows: body composition assessed by bioelectrical impedance; resting energy expenditure (REE) by 30-minute indirect calorimetry; cytokine concentrations (IL-6, IFN alpha, TNF alpha, sTNF-R1) by ELISA; C-reactive protein (CRP), erythrocyte sedimentation rate, fibrinogen, and nutritional parameters by standard techniques. Results: REE adjusted for fat-free mass (REEFFM) was significantly increased in AIDS patients despite 39% of them not being hypermetabolic. The patients were undernourished and were found to have increased levels of acute-phase proteins and increased concentrations of IL-6 and sTNF-R1 relative to controls. REE parameters were positively related to CRP, ESR, ferritin, IL-6, and sTNF-R1 and negatively related to albumin, prealbumin, and transferrin. CRP was an independent predictor of REEFFM in AIDS patients and explained 25% of its variability. Patients with severe inflammation (CRP greater than or equal to 37 mg/dL) were significantly hypermetabolic with respect to patients without inflammation (CRP < 6 mg/dL) and had higher levels of IL-6 and sTNF-R1 and lower levels of albumin and prealbumin. Although no significant differences were observed with respect to the infection type, patients with tuberculosis and Pneumocystis carinii infections had higher resting metabolic and inflammatory responses, whereas patients with recurrent bacterial pneumonia were normometabolic and had lower levels of inflammatory markers. Conclusions: Resting hypermetabolism observed in AIDS patients with concurrent active infections is related to the presence and severity of systemic cytokine-driven inflammatory response, which could reflect the type of secondary infection.