Background: The orexinergic (OXergic) system contributes to the defense system. It has also been reported that the degeneration of OXergic neurons occurs during sepsis. Thus, the decline of OXergic activity may contribute to impairment of the defense system in sepsis. In this study, we determined whether: (i) lipopolysaccharide (LPS) reduces the brain orexin A (OXA) content and (ii) the OXergic system contributes to survival from sepsis in rats. Methods: With approval of our protocol by our University Animal Ethics Committee, OX neuron-ablated (OX/ataxin-3 transgenic [OX/AT3 TG]) and wild-type Sprague-Dawley rats, weighing 250–350 g, were used. LPS (10 mg/kg) was administered intraperitonally to the wild-type rats (group SD, n = 26) and OX/AT3 TG rats (group TG, n = 14). Another 7 SD rats were included as a saline control (group C). Survival analysis was then performed over a period of 3 days. All surviving rats were decapitated and the brain OXA contents (from the cerebrocortex, hippocampus, hypothalamus, and pons) were quantified using ELISA kits. Results: In group SD, 61.5% rats survived, while in group TG, only 21.4% survived (p < 0.05). LPS significantly reduced OXA content (pg/mg of tissue) in group SD (2.92 ± 0.38) compared to in group C (4.10 ± 1.21) in the pons (p < 0.05). OXA content in group TG was substantially lower than in group C and group SD in all brain regions. Conclusions: LPS significantly reduced OXA contents in the pons which contains the locus coeruleus to regulate sympathetic activity in the defense system.

Background Systemic inflammatory response occurs by sepsis and invasive surgery. Recent articles suggest that not only CRP but also procalcitonin, presepsin, and neutrophil gelatinase-associated lipocalin may reflect the severity of systemic inflammation. In addition, as systemic inflammation could degenerate orexin neurons, plasma orexin A might also be a good biomarker to predict the severity. Thus, we have determined relation between plasma biomarker and severity of illness score in patients with systemic inflammation. Methods Previous database (UMIN000018427) was used to secondly determine which plasma biomarkers may predict the severity of illness in the ICU patients with systemic inflammation (n = 57, 31 non-sepsis surgical patients and 26 sepsis patients). We measured plasma levels of orexin A, CRP, procalcitonin, presepsin, and neutrophil gelatinase-associated lipocalin were measured, and APACHE II score was assessed in these patients at their admission to the ICU. Data are shown as mean ± SD. Statistical analyses were done with unpaired t test. The correlation between APACHE II score and plasma biomarkers were examined using Pearson’s correlation coefficient and a least squares linear regression line. Results Demographic data did not differ between sepsis and non-sepsis groups. However, APACHE-II score was significantly higher in sepsis group than those in non-sepsis group (20.9 ± 6.6 vs 15.8 ± 3.2, p < 0.01). There were significant correlations between APACHE II score and plasma CRP (r = 0.532, p < 0.01), procalcitonin (r = 0.551, p < 0.01), presepsin (r = 0.510, p < 0.01), and neutrophil gelatinase-associated lipocalin (r = 0.466, P < 0.01) except orexin A. Conclusion All plasma biomarkers tested except orexin A may reflect the severity of illness in patients with systemic inflammation.

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