{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T18:09:28Z","timestamp":1778522968066,"version":"3.51.4"},"reference-count":95,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The secondary immunomodulatory effects of conventional therapeutics, such as antibiotics and cytostatics, are frequently overlooked despite their significant clinical implications. Building on our previous findings that drugs like paclitaxel and doxorubicin heavily influence macrophage polarization\u2014potentially driving metastasis or inflammation\u2014this study systematically evaluates the secondary immune-modulating actions of standard drugs and natural adjuvants. Using patient-derived bronchoalveolar lavage (BAL) fluid (ex vivo alveolar macrophages), we developed an analytical platform using synthetic carbohydrate-functionalized fluorescent ligands targeting key receptors (CD206, CD209, CD280, CD301). Integrating ligand-binding profiles with Linear Discriminant Analysis (LDA) yielded quantitative immune-state vectors capable of differentiating favorable and unfavorable prognostic signatures and imbalanced immune states. Pro-filing samples across heterogeneous respiratory conditions revealed highly con-text-dependent responses. While some treatments synergistically corrected unfavorable imbalanced profiles, others provoked dysregulation. Notably, in pneumonia or bronchitis with an asthma-prone M2-dominant profile, specific antibiotic regimens are critical; doxycycline, for instance, may exacerbate patient deterioration by further driving M2a polarization. Crucially, we identified that natural adjuvants (e.g., curcumin, coumarins, polyphenols) exhibit potent properties capable of correcting these adverse secondary drug effects. Ultimately, this profiling platform highlights the necessity of evaluating patient-specific secondary drug effects, offering a functional blueprint for precision immunotherapy and the rational design of adjuvant-enhanced treatments.<\/jats:p>","DOI":"10.3390\/ijms27093894","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AI-Driven Secondary Immunomodulatory Effects of Conventional Drugs on Patient-Derived Macrophages"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-0859","authenticated-orcid":false,"given":"Igor D.","family":"Zlotnikov","sequence":"first","affiliation":[{"name":"Laboratory of Targeted Therapy and Differential Diagnosis, Central University, 7 Gasheka St., Moscow 123056, Russia"},{"name":"Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1\/3, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4355-3022","authenticated-orcid":false,"given":"Alexander A.","family":"Vinogradov","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Centre for Mathematical Plasma Astrophysics, KU Leuven, 3001 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9761-7757","authenticated-orcid":false,"given":"Elena V.","family":"Kudryashova","sequence":"additional","affiliation":[{"name":"Laboratory of Targeted Therapy and Differential Diagnosis, Central University, 7 Gasheka St., Moscow 123056, Russia"},{"name":"Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1\/3, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brancewicz, J., W\u00f3jcik, N., Sarnowska, Z., Robak, J., and Kr\u00f3l, M. 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