BACKGROUND: Cell mediated immunity is affected in the course of sepsis and following surgical stress. The natural killer (NK) cells, the granulocytes and the monocytes constitute the immediate unspecific cell mediated immunity. We therefore investigated the effect of surgery- and endotoxin-induced sepsis on NK cells, granulocytes and monocytes in a two-hit model. METHODS: Three groups of 40 mice. Each group was divided into four groups of 10 mice. All the animals were anesthetized and subjected to either: laparotomy; treatment with Escherichia coli endotoxin i.p.; laparotomy followed 20 min later by endotoxin i.p.; or left untreated as a control group. In the first 40 mice the NK cell activity in the spleen and number of NK cells in the liver were measured, in the second the oxidative burst of granulocytes, and in the third the antigen presentation capacity of monocytes. RESULTS: Endotoxin stimulated the NK cell activity and up-regulated the antigen presentation capability on monocytes. In contrast, surgical stress reduced the NK cell activity, the number of NK cells and down-regulated the antigen presentation capability on monocytes. After surgery, followed by administration of endotoxin, the oxidative burst of granulocytes was stimulated while antigen presentation capability on monocytes was down-regulated. Endotoxin prevented or reverted the postoperative suppression of NK cell activity. CONCLUSION: Our two-hit model shows that some cell types of the unspecific immune system exhibit an excessive inflammatory response (NK cells, granulocytes) while specific functions of other cell types (monocytes) are simultaneously diminished. 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.
BACKGROUND: Cell mediated immunity is affected in the course of sepsis and following surgical stress. The natural killer (NK) cells, the granulocytes and the monocytes constitute the immediate unspecific cell mediated immunity. We therefore investigated the effect of surgery- and endotoxin-induced sepsis on NK cells, granulocytes and monocytes in a two-hit model. METHODS: Three groups of 40 mice. Each group was divided into four groups of 10 mice. All the animals were anesthetized and subjected to either: laparotomy; treatment with Escherichia coli endotoxin i.p.; laparotomy followed 20 min later by endotoxin i.p.; or left untreated as a control group. In the first 40 mice the NK cell activity in the spleen and number of NK cells in the liver were measured, in the second the oxidative burst of granulocytes, and in the third the antigen presentation capacity of monocytes. RESULTS: Endotoxin stimulated the NK cell activity and up-regulated the antigen presentation capability on monocytes. In contrast, surgical stress reduced the NK cell activity, the number of NK cells and down-regulated the antigen presentation capability on monocytes. After surgery, followed by administration of endotoxin, the oxidative burst of granulocytes was stimulated while antigen presentation capability on monocytes was down-regulated. Endotoxin prevented or reverted the postoperative suppression of NK cell activity. CONCLUSION: Our two-hit model shows that some cell types of the unspecific immune system exhibit an excessive inflammatory response (NK cells, granulocytes) while specific functions of other cell types (monocytes) are simultaneously diminished. 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.
Authors: Kornél Lakatos; Germán González; Jawad Hoballah; Jeff Brooker; Sinyoung Jeong; Conor Evans; Petra Krauledat; W Peter Hansen; Kevin M Elias; Manish Patankar; Vilmos Fülöp; Panagiotis A Konstantinopoulos; Daniel W Cramer Journal: J Ovarian Res Date: 2022-02-26 Impact factor: 4.234