INVESTIGATION OF THE IMMUNOMODULATORY EFFECTS OF GABAPENTIN ON MAMMALIAN MACROPHAGE CELLS

Abstract

Background. Recent research has increasingly highlighted the intricate crosstalk between the immune and nervous systems, particularly in the context of neurological pathogenesis. Gabapentin, a structural analogue of γ-aminobutyric acid (GABA) conventionally prescribed for epilepsy and neuropathic pain, is now gaining attention for its potential immunomodulatory properties. While it is well established that the nervous, endocrine, and immune systems coordinate through a complex network of shared signaling molecules, the specific impact of gabapentin on macrophages – the primary effectors of innate immunity that also orchestrate adaptive responses via antigen presentation – remains poorly understood. Methods. To elucidate gabapentin’s immunomodulatory capabilities, the murine macrophage cell line J774.2 was exposed to varying concentrations of the drug in the presence or absence of lipopolysaccharide (LPS). Following treatment, the secretion profiles of major inflammatory cytokines, specifically IL-6, TNF-α, IL-12p40, and GM-CSF, were quantified utilizing enzyme-linked immunosorbent assays (ELISA). Results. Our analyses revealed that gabapentin exerted a significant, dose-dependent suppressive effect on the production of IL-6, TNF-α, and IL-12p40 in LPS-stimulated macrophages. Conversely, the secretion of GM-CSF remained largely unaffected. Importantly, none of the tested concentrations induced cytotoxicity, demonstrating that gabapentin effectively dampens the release of pro-inflammatory cytokines without compromising overall macrophage viability. Conclusion. In summary, this study provides compelling evidence for the selective anti-inflammatory and immunomodulatory actions of gabapentin on macrophages. These findings broaden our understanding of gabapentin’s pharmacological profile beyond its classical neurological applications, underscoring its potential therapeutic value in the clinical management of neuroinflammatory and immune-mediated conditions.