Proinflammatory Responses in the Murine Brain after Intranasal Delivery of Cholera Toxin: Implications for the Use of AB Toxins as Adjuvants in Intranasal Vaccines

• Published in: The Journal of infectious diseases Vol. 192; no. 9; pp. 1628 - 1633
• Main Authors: Armstrong, Michelle E. , Lavelle, Ed C. , Loscher, Christine E. , Lynch, Marina A. , Mills, Kingston H. G.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.11.2005; University of Chicago Press; Oxford University Press
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - metabolism; Adjuvants, Immunologic - pharmacology; Administration, Intranasal; Animals; Applied microbiology; Bacteria; Bacterial diseases; Bacteriology; Biological and medical sciences; Biological Transport; Cells, Cultured; Chemokines - genetics; Chemokines - metabolism; Cholera; Cholera Toxin - administration & dosage; Cholera Toxin - metabolism; Cholera Toxin - pharmacology; Cyclooxygenase 2 - metabolism; Female; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Infectious diseases; Interleukin-1 - metabolism; Liver; Medical sciences; Messenger RNA; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; Miscellaneous; Neuroglia; Neuroglia - drug effects; Neuroglia - metabolism; Olfactory bulb; Polymerase chain reaction; RNA, Messenger - genetics; Toxins; Tropical bacterial diseases; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vibrio cholerae; Microbiology; Vibrio cholerae; Rodentia; Central nervous system; Vaccine; Intranasal administration; Encephalon; Infection; Toxin; Vertebrata; Mammalia; Mouse; Immunological adjuvant; Bacteriosis; Bacteria; Vibrionaceae; Cholera
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/491739

Intranasal delivery of vaccines provides an attractive alternative to parenteral delivery, but it requires appropriate mucosal adjuvants. Cholera toxin (CT) is a powerful mucosal adjuvant, but it can undergo retrograde transport to the brain via the olfactory system after intranasal delivery. We demonstrate that intranasal delivery of CT increases the expression of interleukin-1β, cyclooxygenase-2, and chemokine messenger RNA in the murine hypothalamus, whereas parenterally delivered CT has little effect. Our findings suggest that CT can induce proinflammatory mediators in the brain when it is administered intranasally but not parenterally, and they raise concerns about the use of AB toxins as adjuvants in intranasal vaccines.