EFFECTS OF ISOLATED LIMB PERFUSION WITH TUMOR-NECROSIS-FACTOR-ALPHA ON THE FUNCTION OF MONOCYTES AND T-LYMPHOCYTES IN PATIENTS WITH CANCER

The objective of the present study was to investigate the effects of i solated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-al pha) and melphalan in patients with cancer on, first, plasma levels of cytokines, second, systemic monocyte and T-lymphocyte distribution an d, third, the ability of mononuclear cells to produce cytokines upon s timulation in vitro. Six patients undergoing an ILP were entered into the study (group 1). In addition, patients undergoing a major surgical operation (group 2), minor operation (group 3) as well as healthy vol unteers (group 4) were included as control groups. Sensitive enzyme-li nked immunosorbent assays (ELISAs) were used to measure TNF-alpha and interleukin-6 (IL-6) plasma levels at various time points during and a fter operation. Furthermore, the percentage of monocytes and T lymphoc ytes was determined in all studied groups using a FACScan. In addition , cytokine production upon stimulation with lipopolysaccharide (LPS) a nd a combination of anti-CD3/anti-CD28 monoclonal antibodies in whole- blood cultures was investigated. Increased plasma levels of TNF-alpha and IL-6 in patients undergoing ILP was observed, but only IL-6 appear ed to be increased in patients treated with a major operation. No sign ificant fluctuations were found in the other groups studied. Concernin g the number of monocytes, a significant decrease was observed only in patients treated with ILP. Furthermore, a decreased production of TNF -alpha, IL-6 and IL-8 upon various types of stimulation in vitro was f ound in those patients, but also after a major operation. In conclusio n, the results of the present study show increased plasma levels of cy tokines in patients treated with ILP and major operation. Furthermore, a decrease in numbers of monocytes in the circulation and the ability of mononuclear cells to produce cytokines in vitro may be induced by administration of TNF-alpha in ILP. Although similar results were foun d in patients treated with major operation, the underlying mechanisms of this phenomenon remain to be elucidated.