Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conv...

Full description

Saved in:
Bibliographic Details
Main Authors: Mislav Radić, Andrej Belančić, Hana Đogaš, Marijana Vučković, Andrea Gelemanović, Andrea Faour, Ivan Vlak, Josipa Radić
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/14/1/65
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832589362941919232
author Mislav Radić
Andrej Belančić
Hana Đogaš
Marijana Vučković
Andrea Gelemanović
Andrea Faour
Ivan Vlak
Josipa Radić
author_facet Mislav Radić
Andrej Belančić
Hana Đogaš
Marijana Vučković
Andrea Gelemanović
Andrea Faour
Ivan Vlak
Josipa Radić
author_sort Mislav Radić
collection DOAJ
description Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline and doxycycline, exhibit anti-inflammatory and immunomodulatory properties, making them potential supplementary treatments. This narrative review explores their effectiveness, mechanisms of action, safety profiles, and current challenges in RA care. Tetracyclines have demonstrated significant immunomodulatory effects, including the inhibition of pro-inflammatory cytokines and matrix metalloproteinases (MMPs), which are critical in RA pathology. Clinical trials, including double-blind, placebo-controlled studies, have shown efficacy in reducing RA symptoms, particularly in early and refractory cases. However, their use remains limited by inconsistent evidence, small sample sizes, and concerns about antimicrobial resistance. Current guidelines for RA management do not explicitly recommend tetracyclines due to these limitations, although off-label use may be considered in specific cases. The use of tetracycline for RA is restricted by drug interactions causing bacterial resistance alongside unpredictable patient responses, hence the necessity for prudence in its prescription within a clinical setting. To overcome these limitations, the development of safer compounds, in-depth in silico analyses, and integration with personalized medicine approaches are needed. Overall, tetracyclines show promise as adjunct therapies in RA management due to their dual anti-inflammatory and immunomodulatory actions. This review highlights the need for further research to address gaps in evidence, including the development of modified tetracyclines with reduced antimicrobial effects and improved safety profiles, as well as the integration of personalized medicine approaches to optimize patient outcomes.
format Article
id doaj-art-e00c9e644b4d48b8bf2759a9579cd5d1
institution Kabale University
issn 2079-6382
language English
publishDate 2025-01-01
publisher MDPI AG
record_format Article
series Antibiotics
spelling doaj-art-e00c9e644b4d48b8bf2759a9579cd5d12025-01-24T13:18:49ZengMDPI AGAntibiotics2079-63822025-01-011416510.3390/antibiotics14010065Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety InsightsMislav Radić0Andrej Belančić1Hana Đogaš2Marijana Vučković3Andrea Gelemanović4Andrea Faour5Ivan Vlak6Josipa Radić7Department of Internal Medicine, School of Medicine, University of Split, 21000 Split, CroatiaDepartment of Basic and Clinical Pharmacology with Toxicology, Faculty of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, CroatiaDepartment of Neurology, University Hospital of Split, 21000 Split, CroatiaDepartment of Internal Medicine, Division of Nephrology and Dialysis, University Hospital of Split, 21000 Split, CroatiaMediterranean Institute for Life Sciences (MedILS), University of Split, 21000 Split, CroatiaVancouver Coastal Health, Vancouver, BC V5S 1M9, CanadaDepartment of Physical Medicine and Rehabilitation with Rheumatology, University Hospital Split, 21000 Split, CroatiaDepartment of Internal Medicine, School of Medicine, University of Split, 21000 Split, CroatiaRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline and doxycycline, exhibit anti-inflammatory and immunomodulatory properties, making them potential supplementary treatments. This narrative review explores their effectiveness, mechanisms of action, safety profiles, and current challenges in RA care. Tetracyclines have demonstrated significant immunomodulatory effects, including the inhibition of pro-inflammatory cytokines and matrix metalloproteinases (MMPs), which are critical in RA pathology. Clinical trials, including double-blind, placebo-controlled studies, have shown efficacy in reducing RA symptoms, particularly in early and refractory cases. However, their use remains limited by inconsistent evidence, small sample sizes, and concerns about antimicrobial resistance. Current guidelines for RA management do not explicitly recommend tetracyclines due to these limitations, although off-label use may be considered in specific cases. The use of tetracycline for RA is restricted by drug interactions causing bacterial resistance alongside unpredictable patient responses, hence the necessity for prudence in its prescription within a clinical setting. To overcome these limitations, the development of safer compounds, in-depth in silico analyses, and integration with personalized medicine approaches are needed. Overall, tetracyclines show promise as adjunct therapies in RA management due to their dual anti-inflammatory and immunomodulatory actions. This review highlights the need for further research to address gaps in evidence, including the development of modified tetracyclines with reduced antimicrobial effects and improved safety profiles, as well as the integration of personalized medicine approaches to optimize patient outcomes.https://www.mdpi.com/2079-6382/14/1/65rheumatoid arthritistetracyclineminocyclinedoxycycline
spellingShingle Mislav Radić
Andrej Belančić
Hana Đogaš
Marijana Vučković
Andrea Gelemanović
Andrea Faour
Ivan Vlak
Josipa Radić
Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights
Antibiotics
rheumatoid arthritis
tetracycline
minocycline
doxycycline
title Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights
title_full Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights
title_fullStr Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights
title_full_unstemmed Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights
title_short Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights
title_sort tetracyclines in rheumatoid arthritis dual anti inflammatory and immunomodulatory roles effectiveness and safety insights
topic rheumatoid arthritis
tetracycline
minocycline
doxycycline
url https://www.mdpi.com/2079-6382/14/1/65
work_keys_str_mv AT mislavradic tetracyclinesinrheumatoidarthritisdualantiinflammatoryandimmunomodulatoryroleseffectivenessandsafetyinsights
AT andrejbelancic tetracyclinesinrheumatoidarthritisdualantiinflammatoryandimmunomodulatoryroleseffectivenessandsafetyinsights
AT hanađogas tetracyclinesinrheumatoidarthritisdualantiinflammatoryandimmunomodulatoryroleseffectivenessandsafetyinsights
AT marijanavuckovic tetracyclinesinrheumatoidarthritisdualantiinflammatoryandimmunomodulatoryroleseffectivenessandsafetyinsights
AT andreagelemanovic tetracyclinesinrheumatoidarthritisdualantiinflammatoryandimmunomodulatoryroleseffectivenessandsafetyinsights
AT andreafaour tetracyclinesinrheumatoidarthritisdualantiinflammatoryandimmunomodulatoryroleseffectivenessandsafetyinsights
AT ivanvlak tetracyclinesinrheumatoidarthritisdualantiinflammatoryandimmunomodulatoryroleseffectivenessandsafetyinsights
AT josiparadic tetracyclinesinrheumatoidarthritisdualantiinflammatoryandimmunomodulatoryroleseffectivenessandsafetyinsights