Die geschlechtsspezifische Immunantwort nach traumatisch-hämorrhagischem Schock: Vermittlung durch die LPS-Rezeptoren CD14 und TLR4?

Abstract

Background: After trauma and hemorrhagic shock (THS) macrophages obtained from male mice produce significantly lower levels of the proinflammatory cytokines (e. g. IL-1β, IL-6) upon Stimulation with lipopolysaccharide (LPS), whereas females do not show any depression. LPS is known to act via the receptors CD14 and TLR4 on macrophages. However, it is still unknown whether the gender specific immune response after THS is mediated by the different expression of LPS-receptors CD14 and TLR4. Methods: Male and proestrus female mice (C3H/HeN) were subjected to trauma (laparotomy) followed by hemorrhage (mean arterial blood pressure maintained at 35 ± 5 mmHg for 90 min and resuscitation) or sham Operation. Two hours after resuscitation, spieen (SMø) and peritoneal macrophages (PMø) were harvested and cultivated for 2 h. The expression of CD14 and TLR4 was measured by flow cytometry on native SMø and PMø as well as on LPS stimulated macrophages. F4/80 was used as a macrophage marker. Results: The expression of CD14 and TLR4 on SMø) and PMø was not affected by the gender of the animals. No significant difference in the expression of CD14 and TLR4 was evident between males and females. Furthermore, incubation of SMø with LPS did not alter LPS receptor expression in the study groups. Conclusion: Thus, the gender specific cytokine secretion after TSH is not caused by a different LPS receptor density on macrophages of male and female mice. This implicates that different, downstream mechanisms might be responsible for the immunological gender differences observed after THS.