Most low-pathogenicity avian influenza (LPAI) viruses cause no or mild disease in avian species. Little is known about the mechanisms of host defence and the immune responses of avian influenza-infected birds. This study showed that chicken macrophages are susceptible to infection with LPAI H9N2 and H6N2 viruses and that infection led to apoptosis. In H9N2 virus-infected chicken macrophages, Toll-like receptor 7 responded to infection and mediated the cytokine responses. Whilst pro-inflammatory cytokines were largely upregulated, the interferon (IFN) response was fairly weak and IFN-inducible genes were differentially regulated. Among the regulated genes, major histocompatibility complex (MHC) antigens II were downregulated, which also occurred in the lungs of H9N2-infected chickens. Additionally, interleukin (IL)-4, IL-4 receptor and CD74 (MHC class II invariable chain) were also downregulated, all of which are pivotal in the activation of CD4 + helper T cells and humoral immunity. Remarkably, in H9N2virus-infected chickens, the antibody response was severely suppressed. This was in contrast to the robust antibody response in chickens infected with H6N2 virus, in which expression of MHC class II antigens was upregulated. These data suggest that neutralizing antibodies and humoral immunity may not be developed efficiently in H9N2-infected chickens. These findings raise questions about how some LPAI viruses differentially regulate avian immune responses and whether they have similar effects on mammalian immune function.

These data show that neurons in the cortex, thalamus, and reticular formation are similarly depressed by propofol and etomidate. Although anesthetic depression of neuronal activity likely contributes to anesthetic-induced unconsciousness, further work is needed to determine how anesthetic effects at these sites interact to produce unconsciousness.

Background The lamprey spinal cord is a well-characterized vertebrate network that could facilitate our understanding of anesthetic action. We tested several hypotheses concerning the lamprey’s clinical application to anesthesia, and the sites/mechanisms of anesthetic action. Methods In isolated lamprey spinal cords, minimum immobilizing concentrations (MIC) were determined for halothane, isoflurane, sevoflurane, desflurane, propofol, or the nonimmobilizer F6 (1,2-dichlorohexafluorocyclobutane)- applied during D-glutamate-induced fictive swimming or noxious tail stimulation. Isoflurane and propofol effects on fictive swimming were tested in the presence and absence of strychnine and/or picrotoxin. Results Volatile anesthetic MICs were clinically comparable. Isoflurane MIC for fictive swimming and noxious stimulus-evoked movement were the same. F6 did not produce immobility, but decreased the amplitude and phase lag of fictive swimming. Isoflurane decreased fictive swimming cycle frequency, amplitude, autocorrelation, rostrocaudal phase lag, and coherence. Strychnine and picrotoxin elicited only disorganized motor activity under isoflurane and caused small increases in MIC. Propofol’s effects differed from isoflurane for all locomotor rhythm variables except amplitude. The propofol MIC was much larger in lampreys compared to mammals. However, picrotoxin reversed propfol-induced immobility by reinitiating coordinated locomotor activity and increasing MIC >8-fold. Conclusions The lamprey spinal cord is a relevant and tractable vertebrate network model for anesthetic action. Isoflurane disrupts interneuronal locomotor networks. Gamma-aminobutyric acid A and glycine receptors play marginal roles in isoflurane-induced immobility in lampreys. Propofol’s selective gamma-aminobutyric acid AA-receptor-mediated immobilizing mechanism is conserved in lampreys. The differential immobilizing mechanisms of isoflurane versus propofol reflect those in mammals, and further suggest different network modes of immobilizing action.

General anesthetic mechanisms are poorly understood. Anesthetic immobilizing effects occur in the spinal ventral horn. However, a detailed analysis of anesthetic effects on ventral motor networks is lacking. We delivered isoflurane, desflurane, or propofol during NMDA/5-HT-induced, or noxious tail stimulus-evoked, fictive locomotion in neonatal rat isolated spinal cords. Anesthetics changed the frequency, amplitude, and regularity of fictive locomotion with little effect on phase-lag. Isoflurane abolished pharmacologically-induced vs noxious stimulus-induced motor output at similar concentrations. Propofol abolished pharmacologically-induced fictive locomotion via a GABAA-receptor mechanism. Anesthetic effects on pharmacologically-elicted fictive locomotion appear clinically-relevant, and support a ventral horn immobilizing effect on locomotor rhythm generation.

Most low pathogenicity avian influenza (LPAI) viruses cause no or mild diseases in avian species. The H9N2 subtype are commonly detected LPAI viruses that have crossed the species barrier to infect humans, unlike most other LPAI viruses. We report in this study that chicken macrophages are susceptible to infection with H9N2 and H6N2 viruses and infection led to apoptosis. Additionally, in H9N2 virus-infected macrophages, major histocompatibility complex (MHC) antigens, class II in particular, were downregulated, which also occurred in the lungs of H9N2 infected chickens. Pro-inflammatory cytokines and chemokines were differentially regulated in both infected macrophages and lungs. Among the regulated genes, IL-4, IL-4R, and CD74 were downregulated, all of which are pivotal in the activation of CD4+ helper T cells and humoral immunity. Remarkably, in H9N2 virus-infected chickens the antibody response was largely suppressed. This is in contrast to what was observed in those infected with H6N2 virus. This finding suggests that the pathogenesis of H9N2 infection in chickens may involve humoral immune suppression. Modulation of MHC antigens and the subsequent impact on the immune responses in mammals infected with avian influenza viruses is largely unclear. These findings raise questions about how some LPAI viruses regulate avian immune responses and if they have similar effects on mammalian immune function.