Neurotoxicity of Bordetella pertussis.
Pertussis is a unique disease in which the harmful effects are mediated by an exotoxin that effects stimulation of the adrenergic system which is neuronally controlled. The interdependence of the growth of bacteria and toxin production, and the local colonization of the bacteria that precedes the clinical symptom of the disease reflect the nature of the disease. Pertussis toxin enzymatically alters the function of numerous regulatory cells that is demonstrable, after an interval of time, by a specific stimulus. The toxin also may act rapidly and effect action at a target tissue. The latter appears to be associated with the rapid adverse events after vaccination whereas both may occur in the disease. The pathophysiologic responses associated with specific clinical symptoms have not been clearly defined. Responses to be evaluated relative to encephalopathy are increased vascular permeability, hypoglycemia and enhanced activity of neuronal glutamate and aspartate. The intensity of responses is related to the amount of pertussis toxin available, genetic susceptibility, ethnic and allotype, and external factors. The reason for the non-linear dose response shown by the critical level between the sublethal and the lethal infection in mice is unclear. Bacterial adenylate cyclase may be a candidate. Much remains to be elucidated about the enzymatic pathways that effect the many disparate events, the identity of the neurons that effect the clinical symptoms and their CNS location, the identity of the neuronal transmitters and the pathoneuronal pharmacodynamics.
D037361:Adenylate Cyclase Toxin; D000818:Animals; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000503:physiopathology; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000009:adverse effects*; D011956:Receptors, Cell Surface / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000032:analysis / Q000633:toxicity; D014917:Whooping Cough / Q000503:physiopathology*
D037361:Adenylate Cyclase Toxin; D010567:Pertussis Vaccine; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin