{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:31:38Z","timestamp":1753893098479,"version":"3.41.2"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oral Health"],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the combined effects of azithromycin and varying concentrations of cyclosporin on peripheral blood mononuclear cells (PBMCs) under lipopolysaccharide (LPS) stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>PBMCs were isolated from four healthy donors and treated with cyclosporin at concentrations of (50, 200, and 1,000\u2005ng\/ml) either alone or in combination with azithromycin (0.4\u2005\u00b5g\/ml), with and without 100\u2005ng ml LPS derived from Porphyromonas gingivalis. Total cell count, cell viability, and lactate dehydrogenase (LDH) activity were assessed at day 1 and 3. While the inflammatory mediators, including IL-6, IL-1\u03b2, IL-18, and IgA levels were assessed by ELISA at day 3. Statistical analysis included two-way ANOVA to analyze the effects of the drugs and the presence of LPS (the two independent variables), followed by Tukey's HSD <jats:italic>post-hoc<\/jats:italic> test. Multiple linear regression models evaluating treatment effects, LPS exposure, and time points, with assessment of two-way interactions. Models were adjusted for relevant covariates and verified for statistical assumptions, with significance set at <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lower cyclosporin concentrations (50 and 200\u2005ng\/ml) combined with azithromycin maintained higher cell counts and showed reduced cytotoxicity compared to 1,000\u2005ng\/ml under LPS exposure. The 200\u2005ng\/ml cyclosporin-azithromycin combination demonstrated optimal results, reducing IL-6 and IL-1\u03b2 levels while maintaining cell viability. Higher concentrations elevated IgA levels, particularly with LPS stimulation, suggesting enhanced immune response modulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination of azithromycin with moderate cyclosporin concentrations (200\u2005ng\/ml) provides optimal immunomodulatory effects while maintaining cell viability. Higher cyclosporin doses (1,000\u2005ng\/ml) showed increased cytotoxicity despite enhanced immunomodulation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/froh.2025.1544821","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T07:05:40Z","timestamp":1741849540000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of combined cyclosporin and azithromycin treatment on human mononuclear cells under lipopolysaccharide challenge"],"prefix":"10.3389","volume":"6","author":[{"given":"Norah","family":"Alotaibi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aminah","family":"Alesawy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Alalshaikh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal 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