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

J Neuroimmunol. 2003 Mar;136(1-2):25-33. doi: 10.1016/s0165-5728(02)00468-x.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / drug effects
  • Caspase 1 / metabolism
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / pharmacology
  • Female
  • Hypothalamus / drug effects*
  • Hypothalamus / immunology
  • Hypothalamus / metabolism
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Pertussis Vaccine / adverse effects*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-1 / drug effects
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism*
  • Receptors, Interleukin-1 Type I
  • Receptors, Interleukin-1 Type II
  • Sialoglycoproteins / drug effects
  • Sialoglycoproteins / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Pertussis Vaccine
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I
  • Receptors, Interleukin-1 Type II
  • Sialoglycoproteins
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 1