Complex cytokine profiles induced by BCG vaccination in UK infants

Abstract

IFNgamma plays an important part in immunity to tuberculosis (TB), but although it is necessary, it is not on its own sufficient for protection against TB. To identify other cytokines that play a role in the protection against TB induced by BCG vaccination, immune responses were compared between vaccinated and unvaccinated infants from the UK where BCG is known to provide protection. Twenty-one cytokines and chemokines were tested in supernatants from diluted whole blood cultures that had been stimulated for 6 days with Mycobacterium tuberculosis PPD. For 15 out of 21 of the cytokines tested responses were much higher in BCG vaccinated infants than in unvaccinated infants. These included: pro-inflammatory cytokines; IFNgamma (median 1705 pg/ml vs. 1.6 pg/ml in vaccinated and unvaccinated infants, respectively), TNFalpha (median 226 pg/ml vs. 18 pg/ml), as well as IL-2, IL-1alpha and IL-6; TH2 cytokines: IL-4, IL-5 and IL-13 (median 104 pg/ml vs. 1.6 pg/ml); the regulatory cytokine IL-10 (median response 96 pg/ml vs. 8 pg/ml); the TH17 cytokine IL-17, chemokines (IP-10, MIP-1alpha and IL-8) and growth factors (GM-CSF and G-CSF). The greatest increase in cytokine production in BCG vaccinees compared to unvaccinated infants was seen with IFNgamma. While responses for many cytokines were correlated with the IFNgamma response, others including IL-17 and IL-10 were not. The pattern of cytokine induction following BCG vaccination is complex and measurement of one of two cytokines does not reveal the whole picture of vaccine-induced protection.

Fig. 1

Cytokine responses in BCG vaccinated and unvaccinated infants. Cytokines in supernatants from diluted whole blood cultures which were stimulated with M.tb PPD for 6 days were measured using a Multiplex assay in infants who had been BCG vaccinated 3 months previously and in unvaccinated control infants. Pro-inflammatory cytokines IL-1α, IL-2, IL-6, TNFα and IFNγ, TH17 cytokine IL-17, TH2 cytokines IL-4, IL-5, IL-13, chemokines IL-8, IP-10, MIP-1α and growth factors G-CSF, GM-CSF.

Fig. 2

Cytokine correlations in BCG vaccinated. Cytokines were measured using a Multiplex assay in supernatants from diluted whole blood cultures which were stimulated with M.tb PPD for 6 days in infants who had been BCG vaccinated 3 months previously.

Fig. 3

Score values for components 1 and 2. Score values for vaccinated (triangles) and unvaccinated infants (diamonds) for components 1 and 2 from the principal components analysis.