Azithromycin (CP-62993)

Azithromycin reduces about 40% of IL-8 mRNA and protein expression in cystic fibrosis (CF) cells reaching the levels of non-CF cells. Azithromycin results in 50% and 70% reduction of NF-kappaB and AP-1 DNA binding, respectively, leading to levels of non-CF cells. ^[1] Azithromycin significantly enhances the intensity of a co-stimulatory molecule, CD80, on DCs but not CD86 and CD40 in dendritic cells (DCs). Azithromycin significantly increases the production of IL-10 and Clarithromycin (CAM) significantly inhibits the production of IL-6 by DCs. Azithromycin increases IL-10 and CAM decreases IL-2 productions significantly, when naive T cells derived from spleen are co-cultured with DCs treated in advance with LPS and these macrolides. ^[2] Azithromycin selectively inhibits fluid-phase endocytosis of horseradish peroxidase and lucifer yellow in J774 mouse macrophages. Azithromycin delays sequestration of receptor-bound transferrin and peroxidase-anti-peroxidase immune complexes into cell-surface endocytic pits and vesicles. Azithromycin down-regulates cell surface transferrin receptors, but not Fc gamma receptors, by causing a major delay in the accessibility of internalized transferrin receptors to the recycling route, without slowing down subsequent efflux, resulting in redistribution of the surface pool to an intracellular pool. ^[3] Azithromycin inserts into the DOPC lipid bilayer, so as to decrease its cohesion and to facilitate the merging of DPPC into the DOPC fluid matrix. ^[4]