Regulation of peripheral inflammation by the central nervous system

Current Rheumatology Reports

Volumn 12, Issue 5, 2010, Pages 370-378

  Waldburger, Jean Marc ^a   Firestein, Gary S ^b  

^a GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^b NONE

Author keywords

Adenosine; Alpha7 receptor; Cholinergic; Dorsal root reflex; P38; Parasympathetic; Spinal cord; Sympathetic

Indexed keywords

ADENOSINE RECEPTOR STIMULATING AGENT; CHOLINESTERASE INHIBITOR; ETANERCEPT; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; N METHYL DEXTRO ASPARTIC ACID; NICOTINIC RECEPTOR; PROTEIN C FOS; SEMAPIMOD;

ACTION POTENTIAL; ADJUVANT ARTHRITIS; ANTIINFLAMMATORY ACTIVITY; ARTHRITIS; AUTONOMIC NERVOUS SYSTEM FUNCTION; CHOLINERGIC SYSTEM; GENE EXPRESSION; GENE FUNCTION; HOMEOSTASIS; HYPOTHALAMUS HYPOPHYSIS SYSTEM; IMMUNOREGULATION; INFLAMMATION; INNATE IMMUNITY; JOINT DESTRUCTION; NEUROPATHIC PAIN; NEUROTRANSMISSION; NONHUMAN; PERIPHERAL PAW INFLAMMATION; REVIEW; RHEUMATOID ARTHRITIS; SPINAL CORD NERVE CELL; STIMULUS RESPONSE; SYMPATHETIC NERVE; SYNOVITIS; VAGUS NERVE; VAGUS NERVE STIMULATION; VAGUS REFLEX;

ANIMALS; AUTONOMIC NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM; CHOLINERGIC FIBERS; HUMANS; INFLAMMATION; NEURAL PATHWAYS; PERIPHERAL NERVES; REFLEX; RHEUMATIC DISEASES; SPINAL CORD; SPINAL NERVE ROOTS; SYMPATHETIC NERVOUS SYSTEM; SYNOVITIS; VAGUS NERVE;

EID: 78149466069     PISSN: 15233774     EISSN: 15346307     Source Type: Journal    
DOI: 10.1007/s11926-010-0124-z     Document Type: Review

References (48)

1. Rees H, Sluka KA, Westlund KN, Willis WD: Do dorsal root reflexes augment peripheral inflammation? Neuroreport 1994, 5:821-824.
2. Kane D, Lockhart JC, Balint PV, et al.: Protective effect of sensory denervation in inflammatory arthritis (evidence of regulatory neuroimmune pathways in the arthritic joint). Ann Rheum Dis 2005, 64:325-327.
3. Straub RH, Harle P: Sympathetic neurotransmitters in joint inflammation. Rheum Dis Clin North Am 2005, 31:43-59, viii.
4. Borovikova LV, Ivanova S, Zhang M, et al.: Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000, 405:458-462.
5. Tracey KJ: The inflammatory reflex. Nature 2002, 420:853-859.
6. Wang H, Yu M, Ochani M, et al.: Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 2003, 421:384-388.
7. Olincy A, Harris JG, Johnson LL, et al.: Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry 2006, 63:630-638.
8. Draisci G, Iadarola MJ: Temporal analysis of increases in c-fos, preprodynorphin and preproenkephalin mRNAs in rat spinal cord. Brain Res Mol Brain Res 1989, 6:31-37.
9. Sluka KA, Westlund KN: An experimental arthritis in rats: dorsal horn aspartate and glutamate increases. Neurosci Lett 1992, 145:141-144.
10. Schaible HG, Grubb BD, Neugebauer V, Oppmann M: The effects of NMDA antagonists on neuronal activity in cat spinal cord evoked by acute inflammation in the knee joint. Eur J Neurosci 1991, 3:981-991.
11. Lin Q, Wu J, Willis WD: Dorsal root reflexes and cutaneous neurogenic inflammation after intradermal injection of capsaicin in rats. J Neurophysiol 1999, 82:2602-2611.
12. Bong GW, Rosengren S, Firestein GS: Spinal cord adenosine receptor stimulation in rats inhibits peripheral neutrophil accumulation. The role of N-methyl-D-aspartate receptors. J Clin Invest 1996, 98:2779-2785.
13. Sorkin LS, Moore J, Boyle DL, et al.: Regulation of peripheral inflammation by spinal adenosine: role of somatic afferent fibers. Exp Neurol 2003, 184:162-168.
14. Boyle DL, Moore J, Yang L, et al.: Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant-induced arthritis. Arthritis Rheum 2002, 46:3076-3082.
15. Raghavendra V, Tanga FY, DeLeo JA: Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci 2004, 20:467-473.
16. Kim SY, Bae JC, Kim JY, et al.: Activation of p38 MAP kinase in the rat dorsal root ganglia and spinal cord following peripheral inflammation and nerve injury. Neuroreport 2002, 13:2483-2486.
17. Svensson CI, Marsala M, Westerlund A, et al.: Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced spinal pain processing. J Neurochem 2003, 86:1534-1544.
18. Ji RR, Suter MR: p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain 2007, 3:33.
19. Boyle DL, Jones TL, Hammaker D, et al.: Regulation of peripheral inflammation by spinal p38 MAP kinase in rats. PLoS Med 2006, 3:e338.
20. •• Boettger MK, Weber K, Grossmann D, et al.: Spinal TNF-alpha neutralization reduces peripheral inflammation and hyperalgesia and suppresses autonomic responses in experimental arthritis. Arthritis Rheum 2010, 62:1308-1318. This study and the study by Boyle et al. [19] demonstrate that spinal activation by the proinflammatory cytokine TNF increases peripheral arthritis. TNF activates the p38 MAPK in spinal microglial cells. Local administration in the cerebrospinal fluid of a p38 MAPK inhibitor or the anti-TNF agent etanercept attenuates synovial inflammation.
21. Rosas-Ballina M, Tracey KJ: Cholinergic control of inflammation. J Intern Med 2009, 265:663-679.
22. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 1996, 93:1043-1065.
23. Pavlov VA, Ochani M, Gallowitsch-Puerta M, et al.: Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci U S A 2006, 103:5219-5223.
24. • Waldburger JM, Boyle DL, Edgar M, et al.: Spinal p38 MAP kinase regulates peripheral cholinergic outflow. Arthritis Rheum 2008, 58:2919-2921. This study and the study by Bernik et al. show that inhibition of the p38 MAPK pathway in the CNS increases the vagal anti-inflammatory pathway, suggesting that some of the effect of p38 inhibitors is mediated by this central mechanism.
25. Bernik TR, Friedman SG, Ochani M, et al.: Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med 2002, 195:781-788.
26. Borovikova LV, Ivanova S, Nardi D, et al.: Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation. Auton Neurosci 2000, 85:141-147.
27. Evrengul H, Dursunoglu D, Cobankara V, et al.: Heart rate variability in patients with rheumatoid arthritis. Rheumatol Int 2004, 24:198-202.
28. Goldstein RS, Bruchfeld A, Yang L, et al.: Cholinergic antiinflammatory pathway activity and High Mobility Group Box-1 (HMGB1) serum levels in patients with rheumatoid arthritis. Mol Med 2007, 13:210-215.
29. Bruchfeld A, Goldstein RS, Chavan S, et al.: Whole blood cytokine attenuation by cholinergic agonists ex vivo and relationship to vagus nerve activity in rheumatoid arthritis. J Intern Med 2010 Feb 18 (Epub ahead of print).
30. Waldburger JM, Boyle DL, Pavlov VA, et al.: Acetylcholine regulation of synoviocyte cytokine expression by the alpha7 nicotinic receptor. Arthritis Rheum 2008, 58:3439-3449.
31. • van Maanen MA, Stoof SP, van der Zanden EP, et al.: The alpha7 nicotinic acetylcholine receptor on fibroblast-like synoviocytes and in synovial tissue from rheumatoid arthritis patients: a possible role for a key neurotransmitter in synovial inflammation. Arthritis Rheum 2009: 60: 1272-1281. This study and the studies by Bruchfeld et al. [29] and Waldburger et al. [30] show that the a7 nicotinic receptor is expressed in the joints of rheumatoid arthritis patients. a7 Agonists suppress cytokine and chemokine release by peripheral blood mononuclear cells [28] and FLS [29,30], providing a rationale for their clinical development.
32. Shaked I, Meerson A, Wolf Y, et al.: MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase. Immunity 2009, 31:965-973.
33. Pavlov VA, Parrish WR, Rosas-Ballina M, et al.: Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Brain Behav Immun 2009, 23:41-45.
34. van Maanen MA, Lebre MC, van der Poll T, et al.: Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice. Arthritis Rheum 2009, 60:114-122.
35. •• Rosas-Ballina M, Ochani M, Parrish WR, et al.: Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci U S A 2008, 105:11008-11013. This study shows that the anti-inflammatory effects of the cholinergic pathway in organs not directly innervated by the vagus could be mediated by an alternative neuroanatomic route involving catecholaminergic fibers.
36. Grimsholm O, Rantapaa-Dahlqvist S, Dalen T, Forsgren S: Unexpected finding of a marked non-neuronal cholinergic system in human knee joint synovial tissue. Neurosci Lett 2008, 442:128-133.
37. Wang H, Liao H, Ochani M, et al.: Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 2004, 10:1216-1221.
38. de Jonge WJ, van der Zanden EP, The FO, et al.: Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2- STAT3 signaling pathway. Nat Immunol 2005, 6:844-851.
39. Lorton D, Lubahn C, Klein N, et al.: Dual role for noradrenergic innervation of lymphoid tissue and arthritic joints in adjuvantinduced arthritis. Brain Behav Immun 1999, 13:315-334.
40. Straub RH, Rauch L, Fassold A, et al.: Neuronally released sympathetic neurotransmitters stimulate splenic interferon-gamma secretion from T cells in early type II collagen-induced arthritis. Arthritis Rheum 2008, 58:3450-3460.
41. Harle P, Pongratz G, Albrecht J, et al.: An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+ cells. Arthritis Rheum 2008, 58:2347-2355.
42. Malfait AM, Malik AS, Marinova-Mutafchieva L, et al.: The beta2-adrenergic agonist salbutamol is a potent suppressor of established collagen-induced arthritis: mechanisms of action. J Immunol 1999, 162:6278-6283.
43. Straub RH, Gunzler C, Miller LE, et al.: Anti-inflammatory cooperativity of corticosteroids and norepinephrine in rheumatoid arthritis synovial tissue in vivo and in vitro. FASEB J 2002, 16:993-1000.
44. • Fassold A, Falk W, Anders S, et al.: Soluble neuropilin-2, a nerve repellent receptor, is increased in rheumatoid arthritis synovium and aggravates sympathetic fiber repulsion and arthritis. Arthritis Rheum 2009, 60:2892-2901. This paper describes the surprising synergistic nerve repellent effect between semaphoring 3F, a nerve repellent factor, and the soluble form of its receptor neuropilin-2. The measured increase in the concentration of soluble neuropilin-2 in rheumatoid arthritis synovial fluid thus could contribute to the loss of sympathetic fibers in the synovium rather than neutralizing the repellent semaphoring 3F.
45. McGrath J, McDonald JW, Macdonald JK: Transdermal nicotine for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2004, 4:CD004722.
46. Reale M, Iarlori C, Gambi F, et al.: Acetylcholinesterase inhibitors effects on oncostatin-M, interleukin-1 beta and interleukin-6 release from lymphocytes of Alzheimer's disease patients. Exp Gerontol 2005, 40:165-171.
47. Schachter SC: Vagus nerve stimulation: where are we? Curr Opin Neurol 2002, 15:201-206.
48. Briggs CA, Gronlien JH, Curzon P, et al.: Role of channel activation in cognitive enhancement mediated by alpha7 nicotinic acetylcholine receptors. Br J Pharmacol 2009, 158:1486-1494.