Olfactory bulb and hypothalamic acute-phase responses to influenza virus: effects of immunization.
BACKGROUND
Within hours of intranasal challenge, mouse-adapted H1N1 A/Puerto Rico/8/34 (PR8) influenza genomic RNA is found in the olfactory bulb (OB) and OB pro-inflammatory cytokines are up-regulated. Severing the olfactory tract delays the acute-phase response (APR) and the APR is attenuated by immunization.


OBJECTIVE
To determine if immunization affects OB localization of influenza or the molecular brain mechanisms regulating APR.


METHODS
Male mice were immunized with PR8 influenza, then OB viral RNA, APR, and influenza-related cytokine responses were determined after homologous viral challenge.


RESULTS
Immunization did not prevent influenza OB viral invasion within 24 h of viral challenge. However, it greatly attenuated OB viral RNA 6 days after viral challenge and the APR including hypothermia and body weight loss responses. Within the OB, 24 h after influenza challenge, prior immunization blocked virus-induced up-regulation of toll-like receptor 7 and interferon (IFN) γ mRNAs. At this time, hypothalamic (HT) growth hormone-releasing hormone receptor and tumor necrosis factor-α mRNAs were greatly enhanced in immunized but not in positive control mice. By 6 days after viral challenge, OB and HT mRNAs returned towards baseline values. In the lung, mRNA up-regulation was greater than that in the brain and maximized 6 days after challenge. Lung IFNγ mRNA decreased at 24 h but increased 6 days after challenge in the positive compared to negative controls. Immunization prevented the up-regulation of most of the flu-related mRNAs measured in lungs.


CONCLUSIONS
Collectively, these data suggest a role for OB and HT involvement in immunization protection against influenza infection.
Sleep and Performance Research Center and WWAMI Medical Education Program, Washington State University, Spokane, Wash., USA.
Mark R
MR
Zielinski
Gianne
G
Souza
Ping
P
Taishi
Stewart G
SG
Bohnet
James M
JM
Krueger
D000210:Acute-Phase Reaction / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D007031:Hypothalamus / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015213:Neuroimmunomodulation / Q000502:physiology*; D009830:Olfactory Bulb / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D012367:RNA, Viral / Q000032:analysis; D014611:Vaccination
D016207:Cytokines; D007252:Influenza Vaccines; D012367:RNA, Viral