IL-1beta-dependent neurological effects of the whole cell pertussis vaccine: a role for IL-1-associated signalling components in vaccine reactogenicity.

ABSTRACT

Immunization with the whole cell pertussis vaccine (Pw), but not the acellular pertussis vaccine (Pa), is associated with a number of neurological side effects. Previously, we have demonstrated a role for interleukin-1beta (IL-1beta) in Pw reactogenicity. Here we report that parenteral Pw administration resulted in a concomitant increase IL-1 type I receptor (IL-1RI) mRNA and a decrease in IL-1 type II receptor (IL-1RII) mRNA expression in the murine hypothalamus. These Pw-induced changes were accompanied by an increase in caspase-1 and interleukin-1beta (IL-1beta), and were associated with increased activity of the stress-activated kinase, p38. In contrast, immunization with Pa failed to activate pro-inflammatory IL-1 responses but resulted in increased IL-1 receptor antagonist (IL-1ra) production. These results suggest that the neurological effects of Pw are associated with central activation of IL-1beta and IL-1-associated signalling components.