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

Abstract

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.

Increased production of tumor necrosis factor-alpha in whole blood cultures from children with primary malnutrition

“…The sensitivity to low doses of LPS was increased in malnourished children relative to healthy controls. While these findings are consistent with several lines of evidence from the literature (11)(12)(13)(14)(15), they are clearly at variance with those reported by other investigators addressing the same issue in other countries (7,9). It is not clear, at present, whether these discrepancies can be reconciled without further studies, but methodological differences may play a major role.…”

“…Several studies describe a marked deficit in TNF-α, IL-1, and IL-6 production in severe childhood malnutrition (7)(8)(9)(10) while others have reported that starvation increases TNF-α production (11). Furthermore, production of IL-1 and IL-6 is increased in malnourished subjects free from infection (12), and production of TNF-α and IL-1 proceeds normally in animal models of protein malnutrition (13,14). Finally, increased levels of soluble TNF-α receptors, which are induced by sustained increases in TNF-α receptors as part of regulatory mechanisms (15)(16)(17)(18), have been detected in malnourished children (19), suggesting that these children are capable of significant TNF-α production.…”

Metabolism and catabolism in hip fracture patients: Nutritional and anabolic intervention—a review

“…Injuryinduced release of stress hormones and proinflammatory cytokines such as tumour necrosis factor-α, IL-1β and IL-6 may sustain a prolonged catabolic state characterized by nitrogen loss (Weissman 1990, Cederholm et al 1997) and insulin resistance, the latter often presenting as hyperglycemia despite elevated levels of insulin, exacerbating the depletion of muscle protein and lean body mass. Although insulin resistance may be physiological in some situations, it is generally not beneficial for recovery (Thorell et al 1999, van den Berghe et al 2001.…”

Malnutrition in women with rheumatoid arthritis is not revealed by clinical anthropometrical measurements or nutritional evaluation tools

“…In RA as in other chronic diseases, the systemic activity of inflammatory mediators, for example, cytokines as interleukin (IL)-1beta, tumour necrosis factor (TNF) and IL-6 have been indicated as inducers of muscle wasting (Roubenoff et al, 1992;Cederholm et al, 1997). Also the resulting disability has impact on the nutritional status in these patients (Hernandez-Beriain et al, 1996).…”