Immunomodulatory Effects of Macrolide Antibiotics – Part 1: Biological Mechanisms

Abstract

Macrolide antibiotics are well known for their antibacterial and anti-inflammatory properties. This article provides an overview of the biological mechanisms through which macrolides exert this ‘double effect’. Their antibacterial effect consists of the inhibition of bacterial protein synthesis, impaired bacterial biofilm synthesis, and the attenuation of other bacterial virulence factors. Apart from these direct antimicrobial effects, macrolides are known for their modulating effect on many components of the human immune system. By influencing the production of cytokines, they have a dampening effect on the proinflammatory response. Furthermore, the majority of cells involved in the immune response are, in one way or another, influenced when macrolide antibiotics are administered. Having such an obvious effect on the various aspects of the immune system, macrolides seem to be exceptionally suited for the treatment of chronic inflammatory diseases.

Direct and Indirect Anti-Inflammatory Effects of Tulathromycin in Bovine Macrophages: Inhibition of CXCL-8 Secretion, Induction of Apoptosis, and Promotion of Efferocytosis

“…Some macrolide antibiotics are capable of delivering dual antimicrobial and anti-inflammatory benefits (19,34). Mannheimia haemolytica serotype S1, one of the primary causative agents of bovine respiratory disease, produces leukotoxins (LKT) that stimulate the release of inflammatory cytokines and lipid mediators, such as CXCL-8, TNF-␣, and LTB 4 , from alveolar macrophages and neutrophils and cause cell necrosis (15-17, 20, 21, 36, 37).…”

Management of bronchiectasis in adults

“…Alongside their antimicrobial effects, macrolides have anti-inflammatory effects including inhibition of inflammatory cell migration, cytokine secretion and possible attenuation of the production of reactive oxygen species [63,64] Other mechanisms that have been proposed to explain macrolide benefit include reduction of biofilms surrounding virulent Gram-negative organisms such as P. aeruginosa and promotion of gastric emptying that may reduce potential for acid reflux [65,66].…”

Efficacy of Some Antibiotics in Curing Resistant <i>Escherichia coli</i> Infection

“…By influencing the production of cytokines, they have a dampening effect on the proinflammatory response. Having such an obvious effect on the various aspects of the immune system, macrolides seem to be exceptionally suited for the treatment of chronic inflammatory diseases [51] [70].…”