Enhanced generation of interleukins 1 beta and 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 beta 1 (TGF-beta 1), were analyzed in serum (IL-6, IL-1ra, IL-10, TGF-beta 1) and stimulated blood monocytes (IL-1 beta, TNF alpha, IL-6) obtained from elderly patients with protein-energy malnutrition (PEM). Twenty-one uninfected malnourished patients aged 75 +/- 1 y (mean +/- 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-1 beta, TNF-alpha, and IL-6 were determined. Serum concentrations 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 undetectable concentrations, P < 0.01, respectively). Higher generation of IL-1 beta (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 microgram LPS/L. Monocyte TNF generation 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 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-1 beta in malnourished patients may contribute to the PEM often encountered in chronic nonmalignant disorders.
Cederholm
T
T
Karolinska Institute, Stockholm, Sweden. tommy.cederholm@ger.svso.sll.se
Wretlind
B
B
Hellström
K
K
Andersson
B
B
Engström
L
L
Brismar
K
K
Scheynius
A
A
Forslid
J
J
Palmblad
J
J
D000368:Aged; D002100:Cachexia / Q000097:blood*; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008297:Male; D009752:Nutritional Status; D011446:Prospective Studies; D011502:Protein-Energy Malnutrition / Q000097:blood*; D015291:Transforming Growth Factors / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D015291:Transforming Growth Factors