Macrolides and Inflammatory Cells, Signaling, and Mediators

Low-dose long-term macrolide therapy had a remarkable effect on the prognosis of diffuse panbronchiolitis and suppression of airway secretion and neutrophilic inflammation in this disease. Macrolides inhibit airway water secretion, mucin secretion, and mucus production. Macrolides also suppress neutrophilic infiltration through suppression of proinflammatory cytokines, chemokines, and adhesion molecules. However, macrolides do not appear to be immunosuppressive but rather immunomodulatory, to reset and normalize inflammation. In order to elucidate the mechanism of action of macrolides, the intracellular signal transduction mechanism has been investigated using animal models and cell lines, and in these models, it is important to inhibit mitogen-activated protein kinases and transcription factors such as NFκB. However, the effects of macrolides are widespread and diverse, as are their target proteins and receptors. Since macrolides affect lysosome, autophagy, and apoptosis, their affinity with the membranes that constitute the cell membrane and intracellular organelles attracts attention. This can explain many of the actions of macrolides, intracellular accumulation, and temporal transition of actions.