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Microbial Immunity and Vaccines

Whole-Cell but Not Acellular Pertussis Vaccines Induce Convulsive Activity in Mice: Evidence of a Role for Toxin-Induced Interleukin-1β in a New Murine Model for Analysis of Neuronal Side Effects of Vaccination

Sheila Donnelly, Christine E. Loscher, Marina A. Lynch, Kingston H. G. Mills
Sheila Donnelly
Infection and Immunity Group, Institute of Immunology, National University of Ireland, Maynooth, County Kildare, 1 and
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Christine E. Loscher
Infection and Immunity Group, Institute of Immunology, National University of Ireland, Maynooth, County Kildare, 1 and
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Marina A. Lynch
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College, Dublin, 2 Ireland
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Kingston H. G. Mills
Infection and Immunity Group, Institute of Immunology, National University of Ireland, Maynooth, County Kildare, 1 and
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DOI: 10.1128/IAI.69.7.4217-4223.2001
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    Fig. 1.

    Parenteral injection of mice with Pw induces IL-1β production in the brain and increases core body temperature. (A) BALB/c mice, housed at 30°C, were injected with Pw (0.8 U) or PBS, and temperatures were recorded using a biotelemetry system. BALB/c mice were injected with Pw, Pa, or PBS; 2 h and 4 h later, the hippocampus (B and D) and hypothalamus (C and E) were dissected free, and IL-1β protein was quantified by immunoassay (B, C) and IL-1β mRNA was analyzed by reverse transcription-PCR (D and E). Results are mean (SE) values for six mice in each experimental group. ∗, P < 0.05 ; ∗∗, P < 0.01 versus PBS controls.

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    Fig. 2.

    Parenteral injection with Pw, but not with Pa, induces convulsive behavior in mice. BALB/c mice were injected with Pw, Pa, or PBS and 2 h later were placed at 37°C (Pw/37, Pa/37, or PBS/37). Alternatively, mice were left at room temperature after injection of Pw (Pw/rt). (A) Behavioral activity was recorded for a further hour. (B) Mice were sacrificed, and hippocampal IL-1β protein concentrations were determined by immunoassay. (C) Behavioral changes were also recorded after injection of B. pertussis LPS (6 μg), PT (0.1 μg), LPS and PT, Pw, or PBS and exposure to 37°C. Results are mean (SE) values for six mice in each test group. ∗, P < 0.05 ; ∗∗, P < 0.01 ; ∗∗∗, P < 0.001 Pw versus PBS controls.

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    Fig. 3.

    Pw-induced convulsive behavior is attenuated by pretreatment with an ICE inhibitor and abrogated in IL-1RI−/− mice. Mice were injected intraperitoneally with 0.33 μM ICE inhibitor peptide (ICE Inh.) Ac-YVAD-CMK before s.c. administration of Pw. Two hours later, mice were placed at 37°C, and behavioral activity recorded for a further hour (A). Mice were sacrificed, and hippocampal IL-1β protein concentrations were determined by immunoassay (B). IL-1RI−/− (IL-1R1) and wild-type C57BL/6 (C57) mice were injected s.c. with Pw and placed at 37°C 2 h later, and behavioral activity recorded for a further hour (C). Results are mean (SE) values for six mice in each group. ∗ P < 0.05 ; ∗∗, P < 0.01 , Pw versus ICE inhibitor plus Pw or IL-1RI−/− versus C57BL/6 wild-type mice.

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    Fig. 4.

    Parenteral injection with Pw, but not with Pa, inhibited neurotransmitter release. BALB/c mice were injected s.c. with Pw, Pa, or PBS and 2 h later were placed at 37°C. Alternatively, mice were left at room temperature after injection of Pw (Pw/rt). Synaptosomes prepared from hippocampal tissue were assessed for KC1-induced release of endogenous adenosine (A) and GABA (B). Results are mean (SE) values for unstimulated (unstim), KC1-stimulated (stim), and stimulated versus unstimulated (stim vs unstim) for six mice in each test group. ∗, P < 0.05 ; ∗∗, P < 0.01 , Pw versus Pa.

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Whole-Cell but Not Acellular Pertussis Vaccines Induce Convulsive Activity in Mice: Evidence of a Role for Toxin-Induced Interleukin-1β in a New Murine Model for Analysis of Neuronal Side Effects of Vaccination
Sheila Donnelly, Christine E. Loscher, Marina A. Lynch, Kingston H. G. Mills
Infection and Immunity Jul 2001, 69 (7) 4217-4223; DOI: 10.1128/IAI.69.7.4217-4223.2001

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Whole-Cell but Not Acellular Pertussis Vaccines Induce Convulsive Activity in Mice: Evidence of a Role for Toxin-Induced Interleukin-1β in a New Murine Model for Analysis of Neuronal Side Effects of Vaccination
Sheila Donnelly, Christine E. Loscher, Marina A. Lynch, Kingston H. G. Mills
Infection and Immunity Jul 2001, 69 (7) 4217-4223; DOI: 10.1128/IAI.69.7.4217-4223.2001
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