title: The olfactory nerve has a role in the body temperature and brain cytokine responses to influenza virus.
abstract: Mouse-adapted human influenza virus is detectable in the olfactory bulbs of mice within hours after intranasal challenge and is associated with enhanced local cytokine mRNA and protein levels. To determine whether signals from the olfactory nerve influence the unfolding of the acute phase response (APR), we surgically transected the olfactory nerve in mice prior to influenza infection. We then compared the responses of olfactory-nerve-transected (ONT) mice to those recorded in sham-operated control mice using measurements of body temperature, food intake, body weight, locomotor activity and immunohistochemistry for cytokines and the viral antigen, H1N1. ONT did not change baseline body temperature (Tb); however, the onset of virus-induced hypothermia was delayed for about 13 h in the ONT mice. Locomotor activity, food intake and body weights of the two groups were similar. At 15 h post-challenge fewer viral antigen-immunoreactive (IR) cells were observed in the olfactory bulb (OB) of ONT mice compared to sham controls. The number of tumor necrosis factor alpha (TNFalpha)- and interleukin 1beta (IL1beta)-IR cells in ONT mice was also reduced in the OB and other interconnected regions in the brain compared to sham controls. These results suggest that the olfactory nerve pathway is important for the initial pathogenesis of the influenza-induced APR.
authors.affiliation: Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USA.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Leyva-Grado
authors.forename: Lynn
authors.initials: L
authors.lastname: Churchill
authors.forename: Joseph
authors.initials: J
authors.lastname: Harding
authors.forename: James M
authors.initials: JM
authors.lastname: Krueger
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001831:Body Temperature / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis*; D004435:Eating; D006801:Humans; D007150:Immunohistochemistry; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000378:metabolism* / Q000503:physiopathology* / Q000523:psychology / Q000821:virology; D053583:Interleukin-1beta / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009830:Olfactory Bulb / Q000473:pathology; D009832:Olfactory Nerve / Q000473:pathology / Q000503:physiopathology*; D009976:Orthomyxoviridae Infections / Q000378:metabolism* / Q000503:physiopathology* / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha