The effect of surgery followed by endotoxin on the unspecific cell mediated immunity

It is especially the cell mediated immunity that is affected in the course of sepsis and following surgical stress. The NK cells, the granulocytes and the monocytes constitute the immediate unspecific cells mediated immunity. We therefore investigated the effect on NK cells, granulocytes and monocytes of surgery, endotoxin induced sepsis and a two-hit model composed of surgery followed by administration of endotoxin.

Three groups of 40 mice. Each group was divided into four groups of 10 in each. All the animals were anaesthetized and subjected to either (1) laparotomy, (2) treatment with E. coli endotoxin i.p., (3) subjected to laparotomy followed 20 min later by i.p. endotoxin or (4) left untreated as a control group. In the first 40 mice the NK cell activity in spleens and number of NK cells in livers were measured, in the second the oxidative burst of granulocyte and in the third the antigen presentation capacity of monocytes.

Endotoxin stimulated the NK cell activity and up-regulated the antigen presentation on monocytes. In contrast, surgical stress reduced the NK cell activity, the number of NK cells in tissues and down-regulated the antigen presentation on monocytes. After surgery, followed by administration of endotoxin, the oxidative burst of granulocytes was stimulated while antigen presentation on monocytes was down-regulated. Endotoxin prevented or reverted the postoperative suppression of NK cell activity.

Our two-hit model shows that some cell types of the unspecific immune system exhibit an anti-inflammatory response (monocytes) while others at the same time show an excessive inflammatory response (NK cells, granulocytes). This diversity makes a potential therapeutic immunomodulation very complex, as some cell types would need to be down-regulated while others need to be stimulated.

Affiliations

1. Intensive Care Unit, Aarhus University Hospital, Aarhus C, DK-8000, Denmark
   • P Toft
   • , F Dagnaes-Hansen
   • , MS Petersen
   • , E Tonnesen
   •  & HS Jorgensen

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