TUMOR-NECROSIS-FACTOR RECEPTOR LEVELS ARE LINKED TO THE ACUTE-PHASE RESPONSE AND MALNUTRITION IN HUMAN-IMMUNODEFICIENCY-VIRUS-INFECTED PATIENTS

1. Increased release of tumour necrosis factor is thought to contribute to human-immunodeficiency-virus-associated wasting syndrome. Elevated serum concentrations of tumour necrosis factor have, however, mainly been found during acute opportunistic infections and were not correlated with the degree of wasting. This finding may be explained by the paracrine release and the rapid inactivation of tumour necrosis factor. Serum levels of the two recently detected soluble tumour necrosis factor receptor proteins (p55 and p75) are assumed to reflect tumour necrosis factor release. 2. Serum levels of soluble tumour necrosis factor receptors 55 and 75 were measured by an enzyme-linked immunological and biological binding assay in 45 human-immunodeficiency-virus-infected patients and seven healthy control subjects. Patients were followed up for survival. Serum albumin, prealbumin, total iron-binding capacity (transferrin) and C-reactive protein concentrations were measured using standard laboratory methods. Body composition was determined by bioelectrical impedance analysis. 3. Serum concentrations of soluble tumour necrosis factor receptor 55 and 75 were both significantly increased in human-immunodeficiency-virus-infected patients as compared with the healthy control subjects (P<0.05); soluble tumour necrosis factor receptor concentrations were even more increased in patients with elevated C-reactive protein levels (greater than or equal to 5mg/l) as compared with those with normal C-reactive protein levels (<5mg/l; P<0.0001 and P<0.01, respectively). An association was observed between serum soluble tumour necrosis factor receptor 55 and 75 concentration and (i) serum albumin concentration (r=-0.46, P<0.005 and r=-0.63, P<0.001, respectively), (ii) serum prealbumin concentration (r=-0.42, P<0.005 and r=-0.57, P<0.001, respectively), and (iii) serum total iron-binding capacity (transferrin; r=-0.31, P<0.05 and r=-0.44, P<0.005, respectively). A correlation was also found between serum soluble tumour necrosis factor receptor 55 level and the extracellular mass-body cell mass quotient (r=0.63, P<0.001). 4. The present data provide evidence that the tumour necrosis factor system is involved in the genesis of human-immunodeficiency-virus-associated malnutrition. Serum levels of soluble tumour necrosis factor receptors may be useful for diagnosis and management of the wasting syndrome.