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The on-going high mortality from sepsis motivates continuous research for novel therapeutic strategies. Neuropeptide Y (NPY), a sympathetic neurotransmitter, has been shown to increase survival in experimental septic shock in rats. This protective effect might be due to immunological, cardiovascular or thermoregulatory effects. The aim of this study was to examine the in vivo effect of peripherally administered NPY on body temperature, blood pressure and heart rate in endotoxaemic animals. In order to obtain clinically relevant data, various physiological parameters were monitored in parallel via radio-telemetry in chronically intravenously cannulated, freely behaving rats. Rats received a sublethal bolus of lipopolysaccharide (LPS, 100 µg kg −1 I.V.) and the three parameters were continuously recorded for 72 h. Endotoxaemic rats showed a long-lasting hypotension, an initial hypothermia (−0.5 • C), followed by a prolonged febrile phase (+1.6• C 6 h after endotoxin challenge) associated with a decrease of the circadian rhythm amplitude of temperature. Pretreatment with NPY (160 pmol kg −1 I.V. over 75 min) prevented hypotension and significantly stabilized body temperature immediately following the application. The febrile phase was effectively reduced for at least 72 h. These telemetrically obtained findings clearly demonstrate that pretreatment with NPY positively influences two life-threatening symptoms in endotoxaemia and might be a future option for a successful clinical treatment regimen.

We constructed an oral live vaccine based on the attenuated aroA mutant Salmonella enterica serovar Typhimurium strain SL3261 expressing outer membrane proteins F and I (OprF-OprI) from Pseudomonas aeruginosa and investigated it in a mouse model. Strains with in vivo inducible protein expression with the P pacC promoter showed good infection rates and immunogenicity but failed to engender detectable antibodies in the lung. However, a systemic booster vaccination following an oral primary immunization yielded high immunoglobulin A (IgA) and IgG antibody levels in both upper and lower airways superior to conventional systemic or mucosal booster vaccination alone. In addition, the proportion of IgG1 and IgG2a antibodies suggested that the systemic booster does not alter the more TH1-like type of response induced by the oral Salmonella primary vaccination. We conclude that an oral primary systemic booster vaccination strategy with an appropriate mucosal vector may be advantageous in diseases with the risk of P. aeruginosa airway infection, such as cystic fibrosis.

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