# Pre-existing systemic inflammation impairs bacterial clearance in the spleen

## TL;DR

Pre-existing inflammation reduces the spleen's ability to clear bacteria, even though the overall immune response is weakened.

## Contribution

This study is the first to demonstrate that systemic inflammation impairs splenic bacterial clearance in a porcine model of sepsis.

## Key findings

- The splenic venous to arterial bacterial count ratio was significantly lower in pigs with pre-existing inflammation.
- The inflammatory response to E. coli was dampened in pigs pre-exposed to endotoxin.
- Ex vivo bactericidal capacity was not affected by pre-existing inflammation, suggesting intrinsic spleen mechanisms are involved.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s40635-026-00865-w.