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Several classes of antibiotics, particularly macrolides and to some extent quinolones, exert modulatory effects on inflammatory cells. With a growing number of experimental and clinical studies being performed, the relevance of the immunomodulatory actions of antibiotics to the therapy of respiratory infections is discussed in the light of recent reports.Antibiotics, particularly macrolides, exert both stimulatory and inhibitory effects on leukocytes. These effects seem to be related to the activation state of the leukocytes, facilitating bacterial killing as well as the resolution of local inflammation. In community-acquired pneumonia, this may account for the therapeutic benefit of macrolides, even when bacterial eradication is not complete. A variety of effects of macrolides on Pseudomonas aeruginosa, including the inhibition of biofilm matrix, contribute with immunomodulation to the improvement of respiratory function seen with macrolides in cystic fibrosis.Macrolides can facilitate the killing of microorganisms in acute respiratory infections through the stimulation of neutrophil activation. On long-term administration, anti-inflammatory, T helper type 1 lymphocyte-enhancing and biofilm-thinning actions, among others, make macrolides valid therapeutic options in chronic infectious/inflammatory disorders, even for infections with microorganisms that are not completely eradicated.