Enhanced generation of interleukins 1β and 6 may contribute to the cachexia of chronic disease

Abstract

The cachexia of disease may be promoted by proinflammatory cytokines, eg, interleukin (IL) 1β, tumor necrosis factor α (TNF-α), and IL-6. These, as well as some antiinflammatory cytokines, eg, IL-1 receptor antagonist (IL- 1ra), IL-10, and transforming growth factor β1 (TGF-β1), were analyzed in serum (IL 6, IL-1ra, IL-10, TGF-β1) and stimulated blood monocytes (IL-1β, TNFα, IL-6) obtained from elderly patients with protein-energy malnutrition (PEM). Twenty-one uninfected malnourished patients aged 75 ± 1 y (x̄ ± SD), with a body mass index (BMI in kg/m2) of 17.2 ± 0.5 and various noncancer disorders, and 22 healthy matched control subjects aged 72 ± 1 y, with a BMI of 25.4 ± 0.7 (significantly different from patients, P < 0.001), were included. Fifteen patients and their corresponding control subjects were reexamined 3 mo later. Isolated monocytes were stimulated with lipopolysaccharide (LPS) and concentrations of IL-1β. TNF-α and IL-6 were determined. Serum concentrations of IL-6, IL-1ra, IL-10, TGF-β1 and acute- phase reactants were analyzed. Serum concentrations of orosomucoid and IL-6 were higher in the malnourished subjects than in the control subjects (1.14 ± 0.1 compared with 0.8 ± 0.3 g/L, P < 0.001; and 5 ng/L compared with undetectable concentrations, P < 0.01, respectively). Higher generation of IL-1β (2.7-fold; P < 0.05) and IL-6 (3.7-fold; P < 0.05) was found in monocytes from patients with PEM relative to the control subjects when monocytes were stimulated with 0.1 μg LPS/L. Monocyte TNF generation and serum concentrations of IL-10, IL-1ra, and TGF-β1 did not differ. Similar results were obtained at follow up. IL-1ra was negatively correlated with delayed cutaneous hypersensitivity (r = -0.34, P < 0.05). We conclude that enhanced generation of proinflammatory cytokines such as IL-6 and IL-1β in malnourished patients may contribute to the PEM often encountered in chronic nonmalignant disorders.