Background Sepsis-induced immunosuppression impairs bacterial clearance and increases mortality. Liver and spleen macrophages are an essential part of the mononuclear phagocyte system and crucial for bacterial elimination. Systemic inflammation hampers bacterial clearance in the liver. We hypothesized that immunosuppression due to systemic inflammation might lead to decreased bacterial clearance by the spleen. Methods Anesthetized pigs were subjected to an E. coli infusion for three hours in an intensive care setting. The Naive group only received the bacterial infusion (n = 10). The ETX group (n = 10) received an endotoxin infusion for 24 h, inducing systemic inflammation before the E. coli infusion. The Control group (n = 3) received saline instead of endotoxin for 24 h to study the effects of anesthesia alone. Bacterial counts and endotoxin levels were analyzed during the E. coli infusion. The levels of IL-6 and TNF were analyzed, and the piglets’ physiological response was evaluated. Results There was no difference in the bacterial counts in the artery, splenic vein or hepatic vein. However, the splenic venous to arterial bacterial counts ratio at 1–3 h was lower in Naive compared to ETX group (0.54 (0.34–1.07), 0.54 (0.20–0.85), 0.52 (0.21–0.64) vs. 0.77 (0.61–1.06), 0.85 (0.63–0.89), 0.74 (0.53–0.88); p < 0.01), but there was no difference in the animals’ blood ex vivo bactericidal capacity. There was no difference in endotoxin clearance in the spleen between the groups. The peak log IL-6 and TNF levels in response to the E. coli infusion were higher in the Naive compared to the ETX group (3.40 ± 0.41 vs. 2.94 ± 0.43 pg × mL−1 and 3.78 ± 0.68 vs. 2.23 ± 0.36 pg × mL−1; p < 0.05 and p < 0.001, respectively). The respiratory, circulatory and metabolic response to the E. coli infusion was dampened in the animals pre-exposed to endotoxin. Conclusion The splenic bacterial clearance is impaired by pre-existing systemic inflammation, while differences in endotoxin elimination were not detected. The inflammatory and physiological response to bacteremia is diminished during ongoing inflammation. Since the animals’ ex vivo bactericidal capacity was not affected by pre-existing inflammation, our results suggest that inherent mechanisms in the spleen were involved.

Pre-existing systemic inflammation impairs bacterial clearance in the spleen

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2026年2月4日

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Katja Hanslin,
Paul Skorup,
Frida Wilske,
Anders Larsson,
Eva Tano,
Jan Sjölin,
Miklos Lipcsey

摘要

Background

Sepsis-induced immunosuppression impairs bacterial clearance and increases mortality. Liver and spleen macrophages are an essential part of the mononuclear phagocyte system and crucial for bacterial elimination. Systemic inflammation hampers bacterial clearance in the liver. We hypothesized that immunosuppression due to systemic inflammation might lead to decreased bacterial clearance by the spleen.

Methods

Anesthetized pigs were subjected to an E. coli infusion for three hours in an intensive care setting. The Naive group only received the bacterial infusion (n = 10). The ETX group (n = 10) received an endotoxin infusion for 24 h, inducing systemic inflammation before the E. coli infusion. The Control group (n = 3) received saline instead of endotoxin for 24 h to study the effects of anesthesia alone. Bacterial counts and endotoxin levels were analyzed during the E. coli infusion. The levels of IL-6 and TNF were analyzed, and the piglets’ physiological response was evaluated.

Results

There was no difference in the bacterial counts in the artery, splenic vein or hepatic vein. However, the splenic venous to arterial bacterial counts ratio at 1–3 h was lower in Naive compared to ETX group (0.54 (0.34–1.07), 0.54 (0.20–0.85), 0.52 (0.21–0.64) vs. 0.77 (0.61–1.06), 0.85 (0.63–0.89), 0.74 (0.53–0.88); p < 0.01), but there was no difference in the animals’ blood ex vivo bactericidal capacity. There was no difference in endotoxin clearance in the spleen between the groups. The peak log IL-6 and TNF levels in response to the E. coli infusion were higher in the Naive compared to the ETX group (3.40 ± 0.41 vs. 2.94 ± 0.43 pg × mL⁻¹ and 3.78 ± 0.68 vs. 2.23 ± 0.36 pg × mL⁻¹; p < 0.05 and p < 0.001, respectively). The respiratory, circulatory and metabolic response to the E. coli infusion was dampened in the animals pre-exposed to endotoxin.

Conclusion

The splenic bacterial clearance is impaired by pre-existing systemic inflammation, while differences in endotoxin elimination were not detected. The inflammatory and physiological response to bacteremia is diminished during ongoing inflammation. Since the animals’ ex vivo bactericidal capacity was not affected by pre-existing inflammation, our results suggest that inherent mechanisms in the spleen were involved.