Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation.

The cytokines IL-1 beta and TNF-alpha cause cachexia and hypermetabolism in animal models, but their role in human inflammation remains controversial. The relationship between in vitro cytokine production and metabolism was examined in 23 adults with RA and 23 healthy control subjects matched on age, sex, race, and weight. Body composition was measured by multicompartmental analysis of body cell mass, water, fat, and bone mass. Resting energy expenditure (REE) was measured by indirect calorimetry. Cytokine production by PBMC was measured by radioimmunoassay. Usual energy intake, physical activity, disability scores, medication use, and other confounders were also measured. Body cell mass was 13% lower (P < 0.00001), REE was 12% higher (P < 0.008), and physical activity was much lower (P < 0.001) in subjects with RA. Production of TNF-alpha was higher in RA than controls, both before and after stimulation with endotoxin (P < 0.05), while production of IL-1 beta was higher with endotoxin stimulation (P < 0.01). In multivariate analysis, cytokine production was directly associated with REE (P < 0.001) in patients but not in controls. While energy and protein intake were similar in the two groups and exceeded the Recommended Dietary Allowances, energy intake in subjects with RA was inversely associated with IL-1 beta production (P < 0.005). In this study we conclude that: loss of body cell mass is common in RA; cytokine production in RA is associated with altered energy metabolism and intake, despite a theoretically adequate diet; and TNF-alpha and IL-1 beta modulate energy metabolism and body composition in RA.

Malnutrition among hospitalized patients. A problem of physician awareness.

Between 25% and 50% of patients admitted to an acute medical service are malnourished. Physicians are often unaware which patients are admitted at nutritional risk and make no attempt to arrest further nutritional decline until a dramatic deterioration has occurred. We studied all patients admitted to an acute medical ward service before and after their physicians were taught to recognize nutritional deficiency early and to intervene appropriately. During the initial period, the house staff correctly identified two (12.5%) of 16 patients as being malnourished. During the posteducation period, physicians correctly identified all 14 patients admitted at nutritional risk (100%), using a simple screening device that required only routine admission data. In all cases, the appropriate nutritional intervention was subsequently made. Results were further validated using a pretest and posttest, showing a significant improvement in nutritional knowledge. We conclude that physicians are not presently being taught to recognize malnutrition, that such malnutrition is latrogenically worsened in the hospital, and that physician education can effectively correct this problem.

Catabolic effects of high-dose corticosteroids persist despite therapeutic benefit in rheumatoid arthritis.

Although corticosteroids (CS) cause nitrogen wasting in healthy humans, it is not known whether the salutary antiinflammatory and appetite-stimulating effects of CS in inflammatory diseases mitigate this effect. We measured nitrogen balance before, during, and after 3 d of high-dose methylprednisolone therapy in nine patients with flare-ups of rheumatoid arthritis. There was evidence of preexisting somatic protein and fat depletion in seven of nine subjects. Patients were allowed to eat freely on a metabolic ward. Nitrogen balances were -0.89 +/- 1.38 g/d (means +/- SEM) before CS therapy, -5.77 +/- 1.30 g/d during therapy (P less than 0.001), and -3.54 +/- 1.38 g/d after therapy (P less than 0.01) despite increased energy and nitrogen intake and clinical resolution of inflammation during and after the pulse therapy. We conclude that patients with rheumatoid arthritis are often cachectic and high-dose CS cause nitrogen wasting in these patients despite an antiinflammatory and appetite-stimulatory benefit.

Risk of pulmonary aspiration among patients receiving enteral nutrition support.

We investigated the prevalence, incidence, and risk factors for pulmonary aspiration in all tube-fed adult patients over 6 months. Twelve aspiration events occurred among 276 patients (prevalence, 4.4%; 95% confidence interval, 2.2% to 7.6%). The incidence of aspiration was 2.4 per 1000 tube-feeding days (95% confidence interval, 1.2 to 3.9 per 1000). Despite 17% overall mortality, there was no excess mortality and little morbidity associated with aspiration. The major risk factors for aspiration were patient age (p less than .015) and location in the hospital (p less than .008): the probability of aspiration in the intensive care units (n = 113) was 0.9% compared with 4.9% on medical or surgical wards (n = 142), 16.7% among patients transferred from the intensive care unit to the ward (n = 18), and 33% among patients transferred from the ward to the intensive care unit (n = 3). Pulmonary aspiration is an uncommon and generally benign event among enterally supported patients. More frequent aspiration among ward than intensive care unit patients suggests that aspiration is not an inevitable consequence of severe illness, but can be prevented with adequate nursing care and pulmonary precautions. The fear of aspiration is not a sufficient cause to withhold enteral nutrition support in acutely ill patients.

Hypermetabolism and hypercatabolism in Guillain-Barré syndrome.

We studied 21 patients with Guillain-Barré syndrome who demonstrated multiple nutritional risk factors upon admission to an intensive care unit: ventilator dependence (71.4%), adynamic ileus (23.8%), significant weight loss in the 2 weeks before admission (53.0%), antecedent viral illness with gastrointestinal sequelae (43.0%), cranial nerve deficits impairing oral intake and gastrointestinal motility (60%), and depressed serum transferrin (85.7%). Patients are hypermetabolic and hypercatabolic because of endocrine, infectious, and inflammatory components of the disease. High-energy (40 to 45 nonprotein kcal/kg), high-protein (2.0 to 2.5 g/kg) nutrition support appears to exert a favorable effect on visceral protein repletion, nitrogen balance, and resistance to pulmonary infection. Immediate attainment of positive energy balance in these hypermetabolic patients, ideally assessed by indirect calorimetry and followed by high-energy, high-protein feedings, may promote positive nitrogen balance early and attenuate muscle wasting in Guillain-Barré syndrome.

Mechanisms of loss of lean body mass in patients on chronic dialysis.

Patients on chronic dialysis treatment often have reduced lean body mass. Certain aspects of bio-incompatibility in dialysis can be viewed as leading to a chronic inflammatory state. In most chronic inflammatory diseases, loss of mean body mass is independent of reduced caloric intake. However, reduced caloric intake accounts for most of the weight loss in these patients and also dialysis patients. Refeeding is associated with increased fat deposition more than restoration of muscle mass. In addition to reduced caloric intake, patients with rheumatoid arthritis, a classic example of a chronic inflammatory disease, have an elevated resting energy expenditure associated with decreased lean body mass. Elevated cellular tumor necrosis factor (TNF) and IL-1 beta production can be demonstrated in these patients. However, in many dialysis patients, increased cytokine production can be 'normal' or reduced. This takes place as the level of malnutrition increases. Thus, cytokines such as IL-1 and TNF play a decreasing role in the pathogenesis of loss of body mass as malnutrition increases and curtails the synthesis of cytokines. Similar to patients with AIDS, progressive disease in patients on chronic dialysis may exhibit subclinical malnutrition which leads to decreased cytokine production. Reduction in cytokine production can be viewed as a protective mechanism.

Rheumatoid cachexia: depletion of lean body mass in rheumatoid arthritis. Possible association with tumor necrosis factor.

OBJECTIVE: To investigate body composition and serum tumor necrosis factor (TNF) levels in a series of 24 patients with rheumatoid arthritis (RA). METHODS: Body composition assessment by anthropometric measures and bioelectrical impedance. Cytokine determination in serum by ELISA: RESULTS: When compared to United States population norms, 16 of the subjects (67%) were cachectic. In regression models, lean body mass (LBM) was inversely associated with the number of swollen joints (p < 0.025). Elevated TNF-alpha was found in 3 of 5 flaring patients vs 0 of 18 patients with less active disease (p = 0.001). These 3 were all cachectic, while the 2 flaring patients without detectable TNF had normal LBM (p < 0.03). Among the whole group, there was a trend toward increasing disability with decreased LBM after adjusting for joint pain and disease duration (p < 0.07). CONCLUSION: Cachexia is common in RA, and may be cytokine driven. Given the prognostic impact of LBM wasting in other diseases, the effect of rheumatoid cachexia on outcome in RA deserves further study.

Abnormal vitamin B6 status in rheumatoid cachexia. Association with spontaneous tumor necrosis factor alpha production and markers of inflammation.

OBJECTIVE: To compare vitamin B6 levels in rheumatoid arthritis (RA) patients and healthy control subjects. METHODS: We measured levels of vitamin B6 in 23 adults with well-controlled RA, and in 23 healthy control subjects matched for age, sex, race, and weight. RESULTS: Although plasma folate and vitamin B12 concentrations and erythrocyte B6 activity coefficients were similar in the patients and controls, plasma levels of pyridoxal-5'-phosphate (PLP) were lower in the RA patient group (mean +/- SD 46.1 +/- 48.1 versus 69.3 +/- 58.4 nmoles/liter; P < 0.004). In multivariate analyses, PLP was inversely associated with tumor necrosis factor alpha (TNF alpha) production by peripheral blood mononuclear cells (PBMC) (P < 0.001), after adjustment for age, pain score, erythrocyte sedimentation rate, and use of nonsteroidal antiinflammatory drugs. CONCLUSION: PLP levels are reduced in patients with RA. This reduction is associated with TNF alpha production by PBMC.