IL-1beta-dependent neurological effects of the whole cell pertussis vaccine: a role for IL-1-associated signalling components in vaccine reactogenicity.
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.
Armstrong
Michelle E
ME
Immune Regulation Research Group, Department of Biochemistry, Trinity College, Dublin 2, Ireland.
Loscher
Christine E
CE
Lynch
Marina A
MA
Mills
Kingston H G
KH
D000818:Animals; D020170:Caspase 1 / Q000187:drug effects / Q000378:metabolism; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010567:Pertussis Vaccine / Q000009:adverse effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases
D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D010567:Pertussis Vaccine; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020170:Caspase 1