Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination

Background: The timing of host cytokine responses to influenza vaccination is poorly understood. Objectives: We examined serum cytokine kinetics following inactivated trivalent influenza vaccine (TIV) to better understand potential relationships between markers of inflammation and TIV-related side effects. Patients/Methods: Twenty healthy adult subjects received TIV. Cytokines/chemokines were assessed in intervals from 3 hours to 14 days. Antibody titers were measured at baseline and Day 14. Results: Serum cytokine responses to TIV were evident as early as 3 hours post-immunization. Compared to baseline, IFN-γ and IP-10 were significantly elevated 7 hours after TIV administration. Both remained elevated and peaked between 16 and 24 hours before returning to baseline by 44 hours post-vaccination. Although IL-8 levels were variable between subjects during the first 24 hours after TIV, by 44 hours, IL-8 was significantly lower compared to baseline. Interestingly, IL-8 levels remained significantly lower for up to 2 weeks after receiving TIV. Fifteen of 20 subjects reported mild adverse events. The one subject who reported moderate myalgias and injection site pain after vaccination displayed a distinctive, early cytokine response profile which included IL-6, IL-2, IL-8, IP-10, MCP-1, TNF-α, TARC, and MCP-4. Conclusions: Serum cytokines changed rapidly following TIV and generally peaked at 24 hours. Trivalent influenza vaccine-induced reductions in IL-8 occurred later (44 hours) and were sustained for 2 weeks. An outlier response coincided with the only moderate side effects to the vaccine. These data suggest that early cytokine/chemokine responses may provide additional insight into the pathogenesis of adverse events and immune reactivity to vaccination.