Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Wunsch, S.
Interleukin 17 pathway in invasive candidiasis
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medical University of Graz; 2021. pp. 102
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Krause Robert
- Rabensteiner Jasmin
- Zollner-Schwetz Ines
- Altmetrics:
- Abstract:
- Objectives Interleukin (IL) 17A is one of the main cytokines related to Candida-specific immunity. Previous data indicated significantly elevated and time-dependent IL-17A levels in patients with candidemia compared to non-candidemic patients. The aim of the present study was the evaluation of levels and time courses of IL-17A, kynurenine, tryptophan, and other cytokines suggested to be involved in anti-Candida host defense as possible biomarkers for early identification of invasive candidiasis. Methods Plasma cytokine values (IL-6, IL-8, IL-10, Il-17A, IL-17F, IL-22, IL-23 (p19), IFN-ɣ, TNF-α, PTX3, TGF-β) were measured via performance of 11-Plex immunoassay. Kynurenine and tryptophan levels were determined by high-performance liquid chromatography. Serial cytokine measurements were carried out from previous 4 days up to day 14 relative to sampling of the index culture (−4; 14). For comparison of time-dependent courses of cytokine levels between the five study groups [invasive candidiasis (IC (other), IC (true), Staphylococcus aureus bacteremia, Escherichia coli bacteremia, healthy controls] specific time intervals (days) were defined (day 1 = day of index sampling): (-4; -2), (-1; 2), (3; 7), (8; 14). Statistical analyses were calculated for the total study population (i.e., main analysis), and after exclusion of immunocompromised patients and patients with hematologic malignancies (i.e., sensitivity analysis). Results IL-17A values were significantly increased in all patient groups compared to healthy controls. In patients with invasive Candida infections, the highest IL-17A levels were determined around the index sampling day (−1; 2) [median 8.8, IQR 5.4-17.3 pg/ml], whereas significantly lower values were measured prior and after index culture sampling. Patients with IC (other) had significantly lower IL-17A levels compared to IC (true) at time intervals (−1; 2) and (3; 7). However, the comparison of IL-17A values between candidemic and bacteremic patients did not reveal any statistically significant differences. Interestingly, TGF-β values were significantly increased in patients with IC (other) compared to bacteremic patients for time intervals (−1; 2), (3; 7) and (8; 14). On the contrary, the comparison of TGF-β levels between patients with IC (true) and bacteremic patients identified statistically significant differences solely for IC (true) vs. E. coli bacteremia [IC (true) > E. coli for time intervals (−4; −2), (−1; 2) and (3; 7)], not for IC (true) vs. S. aureus bacteremia. However, exclusion of patients with immunosuppressive therapy and patients with hematologic malignancies (i.e., sensitivity analysis) demonstrated significantly higher TGF-β values for patients with IC (true) compared to bacteremic patients (both S. aureus and E. coli) for time intervals (−4; −2), (−1; 2) and (3; 7). Conclusion The time-dependent courses of IL-17A levels between patients with invasive Candida infections and bacteremic patients were not discriminative with respect to the etiology of either invasive Candida or bacterial infections. Accordingly, IL-17A may be valuable as a biomarker for either invasive Candida infections or bacterial blood stream infections rather than solely for invasive candidiasis. Besides, we identified significantly increased TGF-β levels in patients with invasive Candida infections compared to bacteremic patients, proposing a possible significance of TGF-β for differentiation between bacterial and Candida infections.