Production of inflammatory cytokines in response to diphtheria-pertussis-tetanus (DPT), haemophilus influenzae type b (Hib), and 7-valent pneumococcal (PCV7) vaccines

Abstract

Haemophilus influenzae type b (Hib) and 7-valent pneumococcal (PCV7) vaccines both became recommended in Japan in 2010. In this study, cytokine production was investigated in peripheral blood mononuclear cells (PBMCs) cultures stimulated with diphtheria and tetanus toxoids combined with acellular pertussis vaccine (DPT), Hib, and PCV7 separately or concurrent different combinations, all as final off-the-shelf vaccines without the individual vaccine components as controls. Higher IL-1β levels were produced when cultures were stimulated with PCV than with DPT or Hib, and the concurrent stimulation including PCV7 enhanced the production of IL-1β. Although Hib induced higher levels of IL-6, no significant difference was observed in IL-6 production with the concurrent stimulation. The concurrent stimulation with Hib/PCV7 and DPT/Hib/PCV7 produced higher levels of TNF-α and human G-CSF. Cytokine profiles were examined in serum samples obtained from 61 vaccine recipients with febrile reactions and 18 recipients without febrile illness within 24 h of vaccination. No significant difference was observed in cytokine levels of IL-1β, IL-4, IL-6, IL-10, IL-12, IFN-γ, MIP-1, TNF-α, and prostaglandin E2 (PGE2) in sera between the two groups. However, significantly higher levels of human G-CSF were observed in recipients with febrile illness than in those without febrile reactions. Further investigations of the significance of elevated serum G-CSF levels are required in vaccine recipients with febrile illness.

Keywords: 7-valent pneumococcal conjugated vaccine; DPT; Diphtheria and tetanus toxoids combined with acellular pertussis vaccine; Haemophilus influenzaetype b T-conjugated vaccine; Hib; PBMCs; PCV7; cytokine; innate immunity; peripheral blood mononuclear cells.

Figure 1. IL-1β, IL-6, TNF-α, and G-CSF production in PBMCs cultures stimulated with DPT, Hib, PCV7, DPT/Hib, DPT/PCV7, Hib/PCV7, and DPT/Hib/PCV7. PBMCs were obtained from 29 individuals and culture fluids were harvested 24 h after stimulation. Cytokine concentrations were measured using BioPlex 17 cytokine panel. Each bar represents the mean concentration (•) with 95% CI.

Figure 2. IL-1β production in the PBMCs of 29 individuals. PBMCs were stimulated with DPT, Hib, PCV7, DPT/Hib, DPT/PCV7, Hib/PCV7, and DPT/Hib/PCV7. Columns from left to right in each individual show the production of IL-1β measured by EIA.

Figure 3. Cytokine profiles of 61 individuals with febrile reactions within 24 h after immunization (upper panel) and those of 18 recipients without febrile illness (lower panel).