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Synergistic effects of tumour necrosis factor α and lymphotoxin α during lethal endotoxaemia. BJS 2000; 87: 934-934.

Published: 6th December 2002

Authors: M. G. Netea, B. J. Kullberg, I. Verschueren, J. W. M. Van der Meer

Background

Tumour necrosis factor (TNF) α and lymphotoxin (LT) α are members of the TNF family which bind to the same receptors and which play a crucial role in the modulation of the immune response. Their differential and possible redundant roles during lethal endotoxaemia have been investigated in mice deficient in either TNF‐α (TNF–/–) or TNF‐α and LT‐α (TNF–/– LT–/– double knockout) mice.

Method

TNF–/– or TNF–/– LT–/– mice were injected intravenously with Escherichia coli lipopolysaccharide (LPS) 1 or 2 mg per mouse. Circulating levels of interleukin (IL) 1α and 1β were measured 3 h after the LPS challenge, and mortality rates were calculated.

Results

When LPS 1 mg per mouse was used, 80 per cent of the wild‐type mice succumbed, whereas none of the TNF–/– or TNF–/– LT–/– mice died (P < 0·01). However, when LPS 2 mg per mouse was administered, the mortality rate in the control and TNF–/– mice was 100 per cent, whereas none of the TNF–/– LT–/–mice died (P < 0·01), suggesting that the absence of LT‐α has an additional protective effect in lethal endotoxaemia. In comparison to the wild‐type control mice, 3 h after the LPS challenge, the circulating concentrations of IL‐1α were 47 and 55 per cent lower in the TNF–/– and TNF–/– LT–/–mice respectively. Moreover, circulating concentrations of IL‐1β were 40 per cent lower in the TNF–/– mice, but 71 per cent lower in the TNF–/– LT–/– mice compared with the wild‐type controls.

Conclusion

TNF‐α and LT‐α act synergistically during lethal endotoxaemia, and immunomodulation of both TNF‐α and LT‐α should be considered in experimental and clinical settings. © 2000 British Journal of Surgery Society Ltd

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