Antibiotics regulate the immune response in both presence and absence of lipopolysaccharide through modulation of Toll-like receptors, cytokine production and phagocytosis in vitro

• Published in: International immunopharmacology Vol. 18; no. 1; pp. 27 - 34
• Main Authors: Bode, Christian, Diedrich, Britta, Muenster, Stefan, Hentschel, Viktoria, Weisheit, Christina, Rommelsheim, Kuno, Hoeft, Andreas, Meyer, Rainer, Boehm, Olaf, Knuefermann, Pascal, Baumgarten, Georg
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2014
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Cell Line; Cytokines; Cytokines - metabolism; Escherichia coli; Escherichia coli - metabolism; Escherichia coli Infections - drug therapy; Escherichia coli Infections - immunology; Gene Expression Regulation - drug effects; Humans; Immunomodulation; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lipopolysaccharides - immunology; Monocytes - drug effects; Monocytes - immunology; Phagocytosis; Phagocytosis - drug effects; Sepsis; Sepsis - drug therapy; Sepsis - immunology; Toll-like receptors; Toll-Like Receptors - drug effects; Toll-Like Receptors - immunology; Toll-like receptors; Sepsis; Antibiotics; Cytokines; Immunomodulation; Phagocytosis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2013.10.025

The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24h, mRNA levels of both cytokines (IL-1β, IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis. •Antibiotics regulate the TLR- and cytokine expression in an in vitro sepsis model.•These effects are observed in PBMCs from patients with systemic inflammation.•Phagocytic activity of LPS-activated monocytes can be reduced by antibiotics.•Antibiotics differ in their ability to modulate TLR-and cytokine expression.•Moxifloxacin, doxycycline and erythromycin show the strongest modulation effects.