Tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha) and IL-6, when released in excess, have been suggested to be important host mediators of the immunoinflammatory response to injury and infections. Corticosteroids suppress this response in vitro. This study was undertaken to investigate if a single dose of methylprednisolone (MP) could modify the cytokine response in patients undergoing lung surgery. Twenty-one patients with lung cancer were allocated randomly to treatment with MP 30 mg/kg i.v. (MP group) or isotonic saline (control group). Patients were anaesthetized with a balanced anaesthesia combined with thoracic epidural anaesthesia. MP or saline was administered immediately before induction of anaesthesia. The cytokines in plasma were measured by ELISA, and blood samples were collected preoperatively, at the end of surgery, 4 h later, and 1 and 5 days postoperatively. All patients had detectable IL-6 in plasma. Compared to preoperative values, plasma IL-6 levels in the MP group increased from 114 pg/ml (12-350 pg/ml) (mean, range) to peak value 146 pg/ml (15-580 pg/ml) on the first postoperative day. In the control group, IL-6 levels increased from 99 pg/ml (17-350 pg/ml) preoperatively to 125 pg/ml (10-300 pg/ml) on the first postoperative day. The increases were not significant. TNF alpha was detectable in only two patients, one from each group. Low levels of IL-1 alpha were demonstrated in three patients in the MP group and in four patients in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytokines are considered to be important mediators in the pathophysiology of sepsis and septic shock. We investigated if continuous arteriovenous haemofiltration (CAVH) could be used to remove excessive amounts of the cytokines tumour necrosis factor-ex (TNFex), interleukin (/L)-Iex and /L-6 from peripheral blood in critically ill patients. Nine septic patients with renal failure were treated with CAVH. Ultrafittrate and plasma were tested for cytokines by ELISA. All patients had detectable TNFex and IL-6 plasma levels, ranging from /0-750 pg/ml and 50-4,575 pg/ml, respectively. TNFex was removed by the ultrafittrate with concentrations ranging from /0-1,000 pg/ml. The TNFex levels were significantly higher in the ultrafittrate samples than in the corresponding plasma samples (P< 0.003). IL-6 was undetectable in the ultra filtrate from five of the patients despite concomitant high plasma levels. IL-J ex was detectable in both plasma and ultra filtrate in four patients. All patients developed multi-organ faiture and septic shock and seven died. It is concluded that TNFex and /L-Jex but not /L-6 can be removed by CAVH in patients with sepsis.
Infusion of endotoxin elicits lymphopenia and a transient granulocytopenia followed by granulocytosis in peripheral blood. The purpose of this study was to investigate which tissues the lymphocytes are redistributed to in response to endotoxaemia. Lymphocytes were isolated from the peripheral blood of 20 rabbits, labelled with 111Indium-tropolene and reinjected intravenously into the rabbits. Ten rabbits received an infusion of Escherichia coli endotoxin 2 micrograms/kg-1, while 10 rabbits received isotonic saline and served as a control group. The redistribution of lymphocytes was imaged with a gamma camera, and calculated with an interfaced computer before, and 2, 4 and 6 h after infusion of endotoxin or saline. Interleukin-1 beta and serum cortisol were measured. Following endotoxaemia the lymphocytes in peripheral blood decreased from 1.95 10(9)/l to 0.83 6 h later. Interleukin-1 beta and serum cortisol increased significantly. The radioactivity of labelled cells in the spleen and in the heart and lungs decreased to 83.3% and 87.8% of initial values respectively, 6 h after infusion of endotoxin. The radioactivity of the lymphatic tissue in and around the intestine increased to 128.8% of initial values. The results indicate that endotoxaemia induces redistribution of lymphocytes from peripheral blood and spleen to lymphatic tissue.
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