Immunomodulatory activity of phenylephrine on LPS stimulated macrophages

Phenylephrine (PE) acts as a sympathomimetic vasoconstrictor frequently utilized to alleviate nasal blockage via the activation of α-1-adrenergic receptors. This study primarily sought to investigate the drug's potential to influence immune system responses.

The effect of phenylephrine was analyzed by comparing cytokine production levels in LPS-stimulated and unstimulated J774.1 macrophages. The changes in concentrations of IL-6, TNF-α, IL-12p40, and GM-CSF induced by phenylephrine were measured by ELISA.

PE exhibited no intrinsic pro-inflammatory activity, as basal levels of TNF-α, IL-12p40, IL-6, and GM-CSF remained at or near detection limits in PE-only groups. In LPS-stimulated cultures, PE significantly attenuated the inflammatory response across multiple pathways, though the inhibitory patterns varied by cytokine. PE induced a robust, non-dose-dependent inhibition, reducing levels by 40-45% across all concentrations (P < 0.05). A significant dose-dependent suppression was observed, with the maximal dose (10 µg/mL) reducing levels from 9,258 pg/mL to 5,802 pg/mL (P < 0.05). Inhibition followed a non-monotonic trend; concentrations of 1 and 10 µg/mL significantly lowered IL-6 (P < 0.05), while the intermediate 5 µg/mL dose yielded no significant effect. PE mediated modulation was restricted, with significant inhibition occurring only at the highest concentration (10 µg/mL; P < 0.05).

The results indicate that phenylephrine influences inflammatory cytokine production and may have potential clinical relevance regarding immune responses and inflammatory diseases.