Which antibiotics have anti-inflammatory effects?

Fråga: Which antibiotics have anti-inflammatory effects?

Sammanfattning: It is well-established that macrolides and tetracyclines have specific anti-inflammatory effects. Possibly, this could also hold true for e.g. fluoroquinolones, rifampicin and vancomycin.

Svar: In addition to their action on bacteria, many antibiotics are thought to possess anti-inflammatory and/or immunomodulatory properties (1, 2).

The macrolides seem to be the most well-documented group of antibiotics in this regard and their anti-inflammatory effects presumably involve inhibited release of several cytokines and suppressed synthesis of endogenous chemotactic factors (1, 2). Clinically, the immunomodulatory effects of macrolides (erythromycin and clindamycin in particular) have been employed in the treatment of e.g. non-infectious pulmonary diseases and inflammatory skin disorders (1, 3).

Tetracyclines have also been associated with anti-inflammatory effects, and are widely used in the treatment of inflammatory skin diseases. Presumably, the mechanisms involved are similar to those of macrolides, but in addition tetracyclines inhibit metalloproteinases involved in inflammatory damage to proteins of the extracellular matrix (4). To facilitate long-term anti-inflammatory treatment without risking antibiotic resistance, modified tetracyclines lacking antibacterial capacity have been developed and successfully evaluated in animal models (5, 6).

Other antibiotics that have been ascribed specific anti-inflammatory effects include fluoroquinolones (1, 7), rifampicin (1, 8), and vancomycin (9). However, these effects have generally only been investigated in vitro and in animal models, and they are not currently used for treatment of any unequivocally non-bacterial diseases. Tauber SC, Nau R. Immunomodulatory properties of antibiotics. Curr Mol Pharmacol 2008;1(1):68-79 Al-Banna NA, Pavlovic D, Grundling M, Zhou J, Kelly M, Whynot S et al. Impact of antibiotics on the microcirculation in local and systemic inflammation. Clin Hemorheol Microcirc 2013;53(1-2):155-169 Alzolibani AA, Zedan K. Macrolides in chronic inflammatory skin disorders. Mediators Inflamm 2012;2012:159354 Griffin MO, Ceballos G, Villarreal FJ. Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action. Pharmacol Res 2011;63(2):102-107 Altenburg J, de Graaff CS, van der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics - part 1: biological mechanisms. Respiration 2011;81(1):67-74 Edan RA, Luqmani YA, Masocha W. COL-3, a chemically modified tetracycline, inhibits lipopolysaccharide-induced microglia activation and cytokine expression in the brain. PLoS One 2013;8(2):e57827 Dalhoff A. Immunomodulatory activities of fluoroquinolones. Infection 2005;33 Suppl 2:55-70 Yuhas Y, zoulay-Alfaguter I, Berent E, Ashkenazi S. Rifampin inhibits prostaglandin E2 production and arachidonic acid release in human alveolar epithelial cells. Antimicrob Agents Chemother 2007;51(12):4225-4230 Abarbanel DN, Seki SM, Davies Y, Marlen N, Benavides JA, Cox K et al. Immunomodulatory effect of vancomycin on Treg in pediatric inflammatory bowel disease and primary sclerosing cholangitis. J Clin Immunol 2013;33(2):397-406