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Purpose <p>Procalcitonin (PCT) is an acute-phase protein and widely used marker for diagnosing bacterial infection and sepsis, but its physiological role remains incompletely defined. Interleukin-1β (IL-1β) is a critical mediator of the immune response to infection, whose excessive release can drive remote organ injury and dysfunction. Its secretion is therefore tightly controlled. Because other acute-phase proteins have been shown to regulate IL-1β secretion, we investigated whether PCT exerts a similar immunomodulatory effect and whether this influences sepsis severity, particularly in Gram-negative urosepsis.</p> Methods <p>Primary human mononuclear leukocytes were stimulated to induce IL-1β release in the presence or absence of increasing PCT concentrations. In parallel, peak PCT levels, infection source, and causative pathogen were analyzed retrospectively in uroseptic patients in comparison to other septic sources, and related to Sepsis-related Organ Failure Assessment (SOFA) scores and serum lactate concentrations.</p> Results <p>PCT significantly inhibited IL-1β secretion from primary mononuclear leukocytes across the 2.5–75&#xa0;µg/L concentration range. Clinically, the highest PCT peaks occurred in patients with Gram-negative urosepsis. Among these, those with peak PCT values within 2.5–75&#xa0;µg/L had significantly lower SOFA scores and lactate levels—established indicators of sepsis severity and prognosis—compared with patients outside this range.</p> Conclusion <p>Within a defined concentration range, PCT down-regulates IL-1β secretion and is associated with reduced markers of disease severity in Gram-negative urosepsis, compared to other sepsis entities. These findings suggest that pronounced PCT elevations in this setting may represent a protective host response rather than a worse prognosis, pointing to a novel immunomodulatory role of PCT in urosepsis that warrants further investigation.</p> <p>DRKS00037950, retrospectively registered on 22 September 2025.</p>

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High procalcitonin in Gram-negative urosepsis: indicator of immune modulation rather than poor outcome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月27日

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  • Sebastian Petzoldt,
  • Christina Buschhaus,
  • Matthias Hecker,
  • Arne Hauptmann,
  • Florian Wagenlehner,
  • Matthias Wolff,
  • Martin Reichert,
  • Veronika Grau,
  • Andreas Hecker,
  • Markus Weigand,
  • Anca-Laura Amati

摘要

Purpose

Procalcitonin (PCT) is an acute-phase protein and widely used marker for diagnosing bacterial infection and sepsis, but its physiological role remains incompletely defined. Interleukin-1β (IL-1β) is a critical mediator of the immune response to infection, whose excessive release can drive remote organ injury and dysfunction. Its secretion is therefore tightly controlled. Because other acute-phase proteins have been shown to regulate IL-1β secretion, we investigated whether PCT exerts a similar immunomodulatory effect and whether this influences sepsis severity, particularly in Gram-negative urosepsis.

Methods

Primary human mononuclear leukocytes were stimulated to induce IL-1β release in the presence or absence of increasing PCT concentrations. In parallel, peak PCT levels, infection source, and causative pathogen were analyzed retrospectively in uroseptic patients in comparison to other septic sources, and related to Sepsis-related Organ Failure Assessment (SOFA) scores and serum lactate concentrations.

Results

PCT significantly inhibited IL-1β secretion from primary mononuclear leukocytes across the 2.5–75 µg/L concentration range. Clinically, the highest PCT peaks occurred in patients with Gram-negative urosepsis. Among these, those with peak PCT values within 2.5–75 µg/L had significantly lower SOFA scores and lactate levels—established indicators of sepsis severity and prognosis—compared with patients outside this range.

Conclusion

Within a defined concentration range, PCT down-regulates IL-1β secretion and is associated with reduced markers of disease severity in Gram-negative urosepsis, compared to other sepsis entities. These findings suggest that pronounced PCT elevations in this setting may represent a protective host response rather than a worse prognosis, pointing to a novel immunomodulatory role of PCT in urosepsis that warrants further investigation.

DRKS00037950, retrospectively registered on 22 September 2025.