Interleukin-1beta-dependent changes in the hippocampus following parenteral immunization with a whole cell pertussis vaccine.
Neurological side effects are a major cause of concern following immunization with a number of vaccines, especially the whole cell pertussis vaccine (Pw). In this study we report that IL-1beta concentrations were significantly increased in the hippocampus following subcutaneous (s.c.) injection of Pw, and that this was accompanied by increased activity of the stress-activated kinase, c-Jun-N-terminal kinase (JNK) and a decrease in glutamate release. These effects were mimicked by s.c injection of active pertussis toxin (PT) or lipopolysaccharide (LPS). Incubation of hippocampal synaptosomes in the presence of Pw, PT or LPS also resulted in increased JNK activation and decreased glutamate release, effects which were mimicked by IL-1beta and blocked by the IL-1 receptor antagonist (IL-ra). Our observations are consistent with the hypothesis that IL-1beta induced by active bacterial toxins present in vaccine preparations, mediate the neurochemical and perhaps the neurological effects of Pw.
Loscher
C E
CE
Infection and Immunity Group, Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
Donnelly
S
S
Mills
K H
KH
Lynch
M A
MA
D000818:Animals; D001923:Brain Chemistry / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000276:immunology* / Q000378:metabolism*; D007114:Immunization; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D048670:MAP Kinase Kinase 4; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000276:immunology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D012795:Sialoglycoproteins / Q000494:pharmacology; D013574:Synaptosomes / Q000201:enzymology / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000276:immunology / Q000494:pharmacology
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010567:Pertussis Vaccine; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D010566:Virulence Factors, Bordetella; D018698:Glutamic Acid; D037342:Pertussis Toxin; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases