Artikel
Variability of LL-37 plasma concentrations and effects on chemotaxis of neutrophilic granulocytes in patients with polytrauma, sepsis and autoinflammatory diseases
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Veröffentlicht: | 10. Oktober 2016 |
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Gliederung
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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.