Fluoroquinolones beyond bacterial infections: exploring their anti-inflammatory and antiviral potential

Abstract

Fluoroquinolones (FQs) are under growing focus as immunomodulating drugs, traditionally known for their broad-spectrum antibacterial action. This narrative review synthesizes in vitro, in vivo and clinical evidence retrieved from PubMed, ScienceDirect, Scopus , Web of Science and Google Scholar. Particularly by phosphodiesterase (PDE) inhibition, recent studies show how well FQs can alter important inflammatory pathways including mitogen-activated protein kinases (MAPKs), nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), and the cyclic adenosine monophosphate (cAMP) pathway. Implicated in many inflammatory illnesses, these actions reduce pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-8, and IL-17. Their effects on regulatory cytokines including IL-2, IL-4, IL-10, and TGF-β, however, depend on medication type, dose, cell origin, and illness situation. This emphasizes the difficulty of FQ-mediated immune regulation and the need for more investigation to define the fundamental processes.

Recent research has also shown fresh intracellular targets for FQs implicated in autoimmune disorders like psoriasis: phosphoinositide 3-kinase gamma (PI3Kγ) and tyrosine kinase 2 (TYK2). Functionalized FQ derivatives, such as R-2TCBA and 2-AnisCEtA, have shown significant anti-inflammatory activity, mainly through the suppression of macrophage nitric oxide generation, without any antibacterial effects. This implies the possibility of creating non-antimicrobial FQ analogues for therapeutic application in inflammatory illnesses. The therapeutic use of FQs as anti-inflammatory drugs is still limited even if the present body of data is strong and experimental models span human cell lines to animal models and modern molecular methods. To promote the repurposing of FQs for chronic inflammatory diseases, important gaps in clinical research need to be addressed. These comprise elucidation of the cytokine modulation patterns linked with various FQs, generation of non-antimicrobial FQ derivatives to prevent antimicrobial resistance, and more mechanistic research on new intracellular targets such as TYK2 and PI3Kγ. Moreover, thorough safety profiles are required as long-term FQ usage has documented hazards including tendinopathy, neurotoxicity, and cardiac arrhythmias. Ultimately, developing a legal and pharmacological framework for repurposing FQs can hasten their development as effective anti-inflammatory treatments.