ENHANCED GENERATION OF INTERLEUKIN-1-BETA AND INTERLEUKIN-6 MAY CONTRIBUTE TO THE CACHEXIA OF CHRONIC DISEASE

The cachexia of disease may be promoted by proinflammatory cytokines, eg, interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. These, as well as some antiinflammatory cytokines, eg, IL-1 receptor antagonist (IL-1ra), IL-10, and transforming growth factor be ta 1 (TGF-beta 1), were analyzed in serum (IL-6, IL-1ra, IL-10, TGF-be ta 1) and stimulated blood monocytes (IL-1 beta, TNF alpha, IL-6) obta ined from elderly patients with protein-energy malnutrition (PEM). Twe nty-one uninfected malnourished patients aged 75 +/- 1 y <((x)over bar +/- SD)>, with a body mass index (BMI; in kg/m(2)) of 17.2 +/- 0.5 an d 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 c orresponding control subjects were reexamined 3 mo later. Isolated mon ocytes were stimulated with lipopolysaccharide (LPS) and concentration s of IL-1 beta, TNF-alpha, and IL-6 were determined. Serum concentrati ons of IL-6, IL-1ra, IL-10, TGF-beta 1, 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 und etectable concentrations, P < 0.01, respectively). Higher generation o f IL-1 beta (2.7-fold; P < 0.05) and IL-6 (3.7-fold; P < 0.05) was fou nd in monocytes from patients with PEM relative to the control subject s when monocytes were stimulated with 0.1 mu g LPS/L. Monocyte TNF gen eration and serum concentrations of IL-10, IL-1ra, and TGF-beta 1 did not differ. Similar results were obtained at follow-up. IL-1ra was neg atively correlated with delayed cutaneous hypersensitivity (r = -0.34, P < 0.05). We conclude that enhanced generation of proinflammatory cy tokines such as IL-6 and IL-1 beta in malnourished patients may contri bute to the PEM often encountered in chronic nonmalignant disorders.