Dynamics of Interaction Between Erythrocytes and Vascular Endothelium Under IFN-Alpha: An Optical Tweezers Study

Background: Interferon alpha (IFN-α) is an antiviral drug with widespread clinical use. Several studies report its effects on the endothelium, including the regulation of nitric oxide (NO) production. Such effects may cause adverse effects in patients with altered blood microrheology, as the interaction between red blood cells (RBCs) and the endothelium is a key factor governing blood microrheology. This study aimed to investigate the effect of IFN-α on the RBC–endothelium system in vitro. Methods: Human umbilical vein endothelial cells (HUVECs) were used as a model of vascular endothelium; human RBCs were obtained from healthy donors, and the forces of intercellular interactions were measured using optical tweezers. Statistical significance was assessed using the Mann–Whitney U test. Results: In the short-term exposure (15–60 minutes), the addition of IFN-α decreased RBC aggregation forces indirectly via the activation of the capacity of HUVECs to produce signaling molecules. Long-term (24 hours) HUVEC incubation with IFN-α had almost no effect, and long-term IFN-α incubation followed by short-term IFN-α reintroduction resulted in a weaker effect at higher concentrations. In the latter case, RBC–HUVEC adhesion decreased at certain concentrations. The minimal sample size comprised five measurements for each of the three donors at each IFN-α concentration. Conclusions: These findings reveal a complex interplay between interferon, endothelium, and RBCs, which should be considered in certain clinical applications of IFN-α. In particular, short-term endothelial exposure to IFN-α can decrease RBC aggregation, which may be helpful or harmful depending on the clinical condition of the patients. Long-term IFN-α treatment followed by short-term IFN-α exposure can decrease RBC–endothelium adhesion forces, altering blood microrheology.