Erythromycin Inhibits Neutrophil Chemotaxis in Bronchoalveoli of Diffuse Panbronchiolitis: Comment

Erythromycin Inhibits Neutrophil Chemotaxis in Bronchoalveoli of Diffuse Panbronchiolitis: CommentThe mobilization of neutrophils from the intravascular compartment into the respiratory tract is crucial for effective host defense. In other clinical settings, however, such as adult respiratory distress syndrome and chronic lower respiratory tract infection, neutrophils are injurious to the host in terms of generating oxygen radicals and in terms of the action of elastase Thus, excessive inflammation contributes to tissue damage asthma inhalers.

Several researchers have described the inhibitory effect of EM on chemotaxis in vitro and on neutrophil migration into the murine lung in response to Proteus mirabilus in vivo.sl In our present study, we found that treatment with EM significantly reduced the number of intra-pulmonary neutrophils, indicating that, in DPB, EM might act first by reducing neutrophil migration and then by inhibiting inappropriate and excessive inflammation in the lower respiratory tract.

The accumulation of neutrophils is induced by a number of chemotactic mediators, including C5a, IL-1, TNFa, IL-8, granulocyte-CSF, granulocyte-macrophage-CSF, 5,12-dihydroxyeicosa-tetraenoic acid (LTB4), and endotoxin.” We evaluated NCA in pre- and post-EM treatment lavage fluid from DPB patients and found that in post-EM BAL fluid, NCA was significantly reduced, and, interestingly, that this correlated with improvements in neutrophil percentages. In a recent study, Hirata et al found that EM had potently suppressed neutrophil chemilu-minescence (CL) induced by FMLP stimulation. In contrast, phorbol myristate acetate-induced CL was much less affected.

Phorbol myristate acetate activates neutrophils, probably through the activation of protein kinase С. Although the concentration of EM in serum was below the MIC for several pathogenic bacteria, EM was 10- to 25-fold concentrated in neutrophils and alveolar macrophages. All these results indicate that EM acts on the intracellular signal pathway, reduces chemotactic activity directly or indirectly, and plays a crucial role in modulating inflammation in the lungs of patients with DPB, all of the effects from EM are from its action in suppressing the oxidative and proteolytic products of neutrophils.
Our chromatographic data showed that the weight after molecular sieving of three of the fractions closely corresponded to the molecular weights of C5a, interleukin-8, and a lipid-containing substance, this being a lipoxygenase pathway metabolite of arachidonic acid. All chemotactic factors were reduced after EM treatment, suggesting that these factors are important in neutrophil recruitment. Which of these factors, however, is quantitatively the most important in this regard was not determined from our findings in this study. Nevertheless, it is likely that EM prevents airway damage in this disorder by suppressing neutrophil accumulation, as a consequence of reducing NCA in the inflammatory sites in the lung.

This entry was posted in Panbronchiolitis and tagged bronchoalveolar lavage fluid, diffuse panbronchiolitis, erythromycin, neutrophil chemotactic factor.