Proinflammatory cytokine responses correspond with subjective side effects after influenza virus vaccination

Background: Though typically mild, side effects to the influenza virus vaccine are common and may contribute to negative perceptions including the belief that the vaccine can cause the flu. However, the extent to which subjective symptoms correspond with biological response indicators is poorly understood.

Methods: This study examined associations among subjective side effects (soreness at the site of injection and illness-like symptoms), serum proinflammatory cytokines and body temperature a baseline, 1, 2, and 3 days following receipt of trivalent inactivated influenza vaccine (IIV3) in a sample of 56 women 18-40 years in age.

Results: In relation to local reactions, women reporting being very sore at the injection site at 1 day post-vaccination exhibited greater increases in serum TNF-α and MIF in the days following vaccination compared to those with no or mild soreness. In addition, higher basal body temperature was observed in this group compared to other groups (98.7°F versus 98.0-98.1°). In relation to systemic reactions, women endorsing illness-like symptoms (headache, fatigue, nausea, sore throat, dizziness, achiness, or mild fever) exhibited marginally higher IL-6 at baseline (p=0.055) and greater increases in serum MIF at 2 days post-vaccination than those reporting no systemic symptoms. Associations of systemic symptoms with inflammatory responses were not accounted for by concomitant local reactions. As expected, antibody responses to the vaccine were highly similar in women regardless of local or systemic symptoms.

Conclusions: These results are consistent with the notion that subjective reports of local and systemic reactions following vaccination may be predicted by and correspond with biological indicators of inflammatory status, but are not meaningful predictors of antibody responses. To improve adherence to vaccine recommendations, clinicians should provide assurance that such symptoms may be related to normal mild inflammatory responses to the vaccine and do not reflect immunogenicity.