Cytokine Expression Patterns and Single Nucleotide Polymorphisms (SNPs) in Patients with Chronic Borreliosis
by
Tabea M. Hein 1, 
Philip Sander 1, Anwar Giryes 2, Jan-Olaf Reinhardt 3, Josef Hoegel 4 and E. Marion Schneider 1,*
Philip Sander 1, Anwar Giryes 2, Jan-Olaf Reinhardt 3, Josef Hoegel 4 and E. Marion Schneider 1,*
1
Division of Experimental Anesthesiology, University Hospital Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
2
Swiss Medical Clinic AG, Grütstrasse 55, CH-8802 Kilchberg, Switzerland
3
Practice for General Medicine, Sports Medicine, and Endocrinology, Leopoldstraße 17, 75172 Pforzheim, Germany
4
Institute of Human Genetics, Ulm University, Albert-Einstein-Allee 11, D-89081 Ulm, Germany
*
Author to whom correspondence should be addressed.
Antibiotics 2019, 8(3), 107; https://doi.org/10.3390/antibiotics8030107
Received: 30 June 2019 / Revised: 21 July 2019 / Accepted: 25 July 2019 / Published: 30 July 2019
(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)
(1) Background: Genetically based hyperinflammation may play a role in pathogen defense. We here questioned whether alterations in circulating monocytes/macrophages, inflammatory biomarkers and a functional SNP (single nucleotide polymorphisms) of the Interleukin-6 (IL-6) promotor might play a role in patients with persistent, and treatment resistant borreliosis. (2) Methods: Leukocyte subpopulations were studied by flow cytometry; plasma cytokines were determined by a chemiluminescence based ELISA (Immulite®), and genotypes of the IL-6 promotor SNP rs1800795 were determined by pyrosequencing. (3) Results: In a cohort of n = 107 Lyme borreliosis patients, who concomitantly manifested either malignant diseases (group 1), autoimmune disorders (group 2), neurological diseases (group 3), or morbidities caused by multiple other infectious complications (group 4), we found decreased numbers of anti-inflammatory CD163-positive macrophages, elevated concentrations of inflammatory cytokines, and an imbalance of IL-6 promotor SNP rs1800795 genotypes. The most prominently upregulated cytokines were IL-1β, and IL-8. (4) Conclusions: Increased pro-inflammatory phenotypes identified by monocyte/macrophage subtypes and concomitantly increased cytokines appear to be valid to monitor disease activity in patients with persistent Lyme borreliosis. Patterns may vary by additional co-morbidities. In patients with autoimmune diseases, increased frequencies of a heterozygous IL-6 promotor SNP rs1800795 were identified. This functional SNP may guide chronic inflammation, impacting other cytokines to trigger trigger chronicity and therapeutic resistance in Lyme borreliosis.
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Keywords:
Lyme borreliosis; CD163; IL-1β; IL-6; IL-8; TNF-α; pro-inflammatory cytokines; IL-6 promotor SNP rs1800795; persisters; pathogens
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MDPI and ACS Style
Hein, T.M.; Sander, P.; Giryes, A.; Reinhardt, J.-O.; Hoegel, J.; Schneider, E.M. Cytokine Expression Patterns and Single Nucleotide Polymorphisms (SNPs) in Patients with Chronic Borreliosis. Antibiotics 2019, 8, 107.
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