Skip to main content Accessibility help
  • Print publication year: 2013
  • Online publication date: October 2013

Chapter 22 - Neuroimmunomodulation in sepsis

from Section 3 - Biological Mechanisms


1. JanBU, CoyleSM, MacorMA, et al. Relationship of basal heart rate variability to in vivo cytokine responses after endotoxin exposure. Shock 2010;33(4):363–8.
2. GalliSJ, BorregaardN, WynnTA. Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nat Immunol 12(11):1035–44.
3. LauneyY, NesselerN, MalledantY, et al. Clinical review: fever in septic ICU patients – friend or foe?Crit Care 2011;15(3):222.
4. BlatteisCM. The onset of fever: new insights into its mechanism. Prog Brain Res 2007;162:3–14.
5. BessacBF, JordtSE. Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology (Bethesda) 2008;23:360–70.
6. LaiCJ, RuanT, KouYR. The involvement of hydroxyl radical and cyclooxygenase metabolites in the activation of lung vagal sensory receptors by circulatory endotoxin in rats. J Appl Physiol 2005;98(2):620–8.
7. NiijimaA. The afferent discharges from sensors for interleukin 1 beta in the hepatoportal system in the anesthetized rat. J Auton Nerv Syst 1996;61(3):287–91.
8. BinshtokAM, WangH, ZimmermannK, et al. Nociceptors are interleukin-1beta sensors. J Neurosci 2008;28(52):14062–73.
9. KonsmanJP, LuheshiGN, BlutheRM, et al. The vagus nerve mediates behavioural depression, but not fever, in response to peripheral immune signals; a functional anatomical analysis. Eur J Neurosci 2000;12(12):4434–46.
10. WillisCL, GarwoodCJ, RayDE. A size selective vascular barrier in the rat area postrema formed by perivascular macrophages and the extracellular matrix. Neuroscience 2007;150(2):498–509.
11. LaflammeN, RivestS. Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J 2001;15(1):155–63.
12. KonsmanJP, KelleyK, DantzerR. Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1beta and inducible nitric oxide synthase in rat brain. Neuroscience 1999;89(2):535–48.
13. KonsmanJP, VeenemanJ, CombeC, et al. Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide. Eur J Neurosci 2008;28(12):2499–510.
14. KonsmanJP, ViguesS, MackerlovaL, et al. Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity: relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli. J Comp Neurol 2004;472(1):113–29.
15. ChingS, ZhangH, BelevychN, et al. Endothelial-specific knockdown of interleukin-1 (IL-1) type 1 receptor differentially alters CNS responses to IL-1 depending on its route of administration. J Neurosci 2007;27(39):10476–86.
16. NgSW, ZhangH, HegdeA, et al. Role of preprotachykinin-A gene products on multiple organ injury in LPS-induced endotoxemia. J Leukoc Biol 2008;83(2):288–95.
17. HegdeA, TamizhselviR, ManikandanJ, et al. Substance P in polymicrobial sepsis: molecular fingerprint of lung injury in preprotachykinin-A-/- mice. Mol Med 2010;16(5–6):188–98.
18. ElenkovIJ, WilderRL, ChrousosGP, et al. The sympathetic nerve – an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000;52(4):595–638.
19. NanceDM, SandersVM. Autonomic innervation and regulation of the immune system (1987–2007). Brain Behav Immun 2007;21(6):736–45.
20. MaddensM, SowersJ. Catecholamines in critical care. Crit Care Clin 1987;3(4):871–82.
21. HahnPY, WangP, TaitSM, et al. Sustained elevation in circulating catecholamine levels during polymicrobial sepsis. Shock 1995;4(4):269–73.
22. YangS, KooDJ, ZhouM, et al. Gut-derived norepinephrine plays a critical role in producing hepatocellular dysfunction during early sepsis. Am J Physiol Gastrointest Liver Physiol 2000;279(6):G1274–81.
23. SpenglerRN, AllenRM, RemickDG, et al. Stimulation of alpha-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor. J Immunol 1990;145(5):1430–4.
24. ZhangF, WuR, QiangX, et al. Antagonism of alpha2A-adrenoceptor: a novel approach to inhibit inflammatory responses in sepsis. J Mol Med (Berl) 2010;88(3):289–96.
25. FlierlMA, RittirschD, Huber-LangM, et al. Catecholamines-crafty weapons in the inflammatory arsenal of immune/inflammatory cells or opening pandora’s box?Mol Med 2008;14(3–4):195–204.
26. DePaceDM, WebberRH. Electrostimulation and morphologic study of the nerves to the bone marrow of the albino rat. Acta Anat (Basel) 1975;93(1):1–18.
27. BenschopRJ, Rodriguez-FeuerhahnM, SchedlowskiM. Catecholamine-induced leukocytosis: early observations, current research, and future directions. Brain Behav Immun 1996;10(2):77–91.
28. DimitrovS, LangeT, BornJ. Selective mobilization of cytotoxic leukocytes by epinephrine. J Immunol 2010;184(1):503–11.
29. OberbeckR, SchmitzD, WilsenackK, et al. Adrenergic modulation of survival and cellular immune functions during polymicrobial sepsis. Neuroimmunomodulation 2004;11(4):214–23.
30. MonastraG, SecchiEF. Beta-adrenergic receptors mediate in vivo the adrenaline inhibition of lipopolysaccharide-induced tumor necrosis factor release. Immunol Lett 1993;38(2):127–30.
31. van der PollT, CoyleSM, BarbosaK, et al. Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 1996;97(3):713–19.
32. JanBU, CoyleSM, OikawaLO, et al. Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: a randomized controlled trial. Ann Surg 2009;249(5):750–6.
33. DunserMW, HasibederWR. Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress. J Intensive Care Med 2009;24(5):293–316.
34. SchmitzD, WilsenackK, LendemannsS, et al. Beta-adrenergic blockade during systemic inflammation: impact on cellular immune functions and survival in a murine model of sepsis. Resuscitation 2007;72(2):286–94.
35. NakamuraA, NiimiR, YanagawaY. Renal beta2-adrenoceptor blockade worsens the outcome of an induced Escherichia coli renal infection. J Nephrol 2010;23(3):341–9.
36. SuzukiT, MorisakiH, SeritaR, et al. Infusion of the beta-adrenergic blocker esmolol attenuates myocardial dysfunction in septic rats. Crit Care Med 2005;33(10):2294–301.
37. HagiwaraS, IwasakaH, MaedaH, et al. Landiolol, an ultrashort-acting beta1-adrenoceptor antagonist, has protective effects in an LPS-induced systemic inflammation model. Shock. 2009;31(5):515–20.
38. MoriK, MorisakiH, YajimaS, et al. Beta-1 blocker improves survival of septic rats through preservation of gut barrier function. Intensive Care Med 2011;37(11):1849–56.
39. HustonJM, TraceyKJ. The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy. J Intern Med 2011;269(1):45–53.
40. StandishA, EnquistLW, EscardoJA, et al. Central neuronal circuit innervating the rat heart defined by transneuronal transport of pseudorabies virus. J Neurosci 1995;15(3 Pt 1):1998–2012.
41. Ter HorstGJ, HautvastRW, De JongsteMJ, et al. Neuroanatomy of cardiac activity-regulating circuitry: a transneuronal retrograde viral labelling study in the rat. Eur J Neurosci 1996;8(10):2029–41.
42. CanoG, PasserinAM, SchiltzJC, et al. Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure. J Comp Neurol 2003;460(3):303–26.
43. ZhangYH, LuJ, ElmquistJK, et al. Lipopolysaccharide activates specific populations of hypothalamic and brainstem neurons that project to the spinal cord. J Neurosci 2000;20(17):6578–86.
44. ElmquistJK, SaperCB. Activation of neurons projecting to the paraventricular hypothalamic nucleus by intravenous lipopolysaccharide. J Comp Neurol 1996;374(3):315–31.
45. HornT, WilkinsonMF, LandgrafR, et al. Reduced febrile responses to pyrogens after lesions of the hypothalamic paraventricular nucleus. Am J Physiol 1994;267(1 Pt 2):R323–8.
46. CaldwellFT, GravesDB, WallaceBH. Studies on the mechanism of fever after intravenous administration of endotoxin. J Trauma 1998;44(2):304–12.
47. LuJ, ZhangYH, ChouTC, et al. Contrasting effects of ibotenate lesions of the paraventricular nucleus and subparaventricular zone on sleep-wake cycle and temperature regulation. J Neurosci 2001;21(13):4864–74.
48. YilmazMS, MillingtonWR, FelederC. The preoptic anterior hypothalamic area mediates initiation of the hypotensive response induced by LPS in male rats. Shock 2008;29(2):232–7.
49. CanoG, SvedAF, RinamanL, et al. Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing. J Comp Neurol 2001;439(1):1–18.
50. DenesA, BoldogkoiZ, UhereczkyG, et al. Central autonomic control of the bone marrow: multisynaptic tract tracing by recombinant pseudorabies virus. Neuroscience 2005;134(3):947–63.
51. JansenAS, WessendorfMW, LoewyAD. Transneuronal labeling of CNS neuropeptide and monoamine neurons after pseudorabies virus injections into the stellate ganglion. Brain Res 1995;683(1):1–24.
52. WesterhausMJ, LoewyAD. Central representation of the sympathetic nervous system in the cerebral cortex. Brain Res 2001;903(1–2):117–27.
53. SwansonLW. Brain Maps: Structure of the Rat Brain. 2nd edn. Amsterdam: Elsevier; 1998.