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.