gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2016)

25.10. - 28.10.2016, Berlin

Variability of LL-37 plasma concentrations and effects on chemotaxis of neutrophilic granulocytes in patients with polytrauma, sepsis and autoinflammatory diseases

Meeting Abstract

  • presenting/speaker Lena Notbohm - Uniklinik Ulm, Klinik für Allgemein- und Viszeralchirurgie, Ulm, Germany
  • Manfred Weiss - Uniklinik Ulm, Sektion Experimentelle Anästhesie, Ulm, Germany
  • Stephanie Denk - Uniklinik Ulm, Klinik für Chirurgie III, Ulm, Germany
  • Markus Huber-Lang - Uniklinik Ulm, Klinik für Chirurgie III, Ulm, Germany
  • Marion E. Schneider - Uniklinik Ulm, Sektion Experimentelle Anästhesie, Ulm, Germany
  • Stephan Paschke - Uniklinik Ulm, Klinik für Allgemein- und Viszeralchirurgie, Ulm, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2016). Berlin, 25.-28.10.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocPO18-1504

doi: 10.3205/16dkou623, urn:nbn:de:0183-16dkou6235

Veröffentlicht: 10. Oktober 2016

© 2016 Notbohm et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: Inflammation either induced by trauma or infections may lead to increased concentrations of the pore forming peptide, LL-37.

Methods: Using ELISA techniques, we determined inflammatory cytokines, lipopolysaccharide binding protein (LBP), ferritin, HMGB1 and LL-37 concentrations in patients with trauma, sepsis/septic shock, and in patients with autoinflammatory diseases and macrophage activation syndromes.

The differential effect by mechanical stress stimuli on LL-37 plasma concentrations was tested by measuring LL-37 before and after intubation and extubation managements in intensive care patients with and w/o concomittant infectious complications.

Isolated neutrophils of patients were tested for chemotaxis against synthetic LL-37 (0.2-2 ng/ml), recombinant C5a (1-10ng/ml) and recombinant IL-8 (10-50 ng/ml).

Results and Conclusion: Highest concentrations of LL-37 were detected in polytrauma patients (5-30 ng/ml). Autoinflammatory diseases and macrophage activation syndromes (MAS) presented with high LL-37 as well (up to 20 ng/ml) and septic patients ranged in between.

In contrast to severe trauma and infections as well as inflammasome activation, intubation and extubation caused only a slight increase of plasma LL-37 (+/- 80-280 pg/ml).

Despite of a high variability in different patients, all patients' derived PMN were more active in migration than neutrophils prepared from healthy donors. When 0.2-2 ng/ml of LL-37 were added into the migration assay, the chemotactic response by the majority of sepsis isolates was impaired by additional LL-37, whereas healthy donors had an increased chemotactic response when LL-37 was present.

Results suggest that LL-37 is a biomarker and effector of sterile as well as infection-associated inflammation. Significant concentrations of LL-37 may impair the chemotactic response of LL-37 against other stimuli. LL-37 synergistically activates chemotaxis in healthy donors but attenuates migration in an infectious microenvironment. Moreover, increased plasma concentration of LL-37 in inflammasome-driven autoinflammatory diseases may explain neutrophilia, vasculitis and skin manifestation.