Tocilizumab attenuates inflammation in ALS patients through inhibition of IL6 receptor signaling

American Journal of Neurodegenerative Diseases

Volumn 1, Issue 3, 2012, Pages 305-315

  Mizwicki, Mathew T ^a   Fiala, Milan ^a   Magpantay, Larry ^a   Aziz, Najib ^a   Sayre, James ^b   Liu, Guanghao ^a   Siani, Avi ^a   Chan, Derrick ^a   Martinez Maza, Otoniel ^a   Chattopadhyay, Madhuri ^c   La Cava, Antonio ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Amyotrophic lateral sclerosis (ALS); Chronic inflammation; IL6 receptor signaling; Tocilizumab

Indexed keywords

ARACHIDONATE 5 LIPOXYGENASE; C REACTIVE PROTEIN; CD14 ANTIGEN; CXCL2 CHEMOKINE; CXCL3 CHEMOKINE; EPITHELIAL DERIVED NEUTROPHIL ACTIVATING FACTOR 78; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HISTONE DEACETYLASE 4; INTERLEUKIN 12; INTERLEUKIN 17; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 5; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; INTERLEUKIN 7; INTERLEUKIN 8; INTERSTITIAL COLLAGENASE; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROSTAGLANDIN SYNTHASE; RETINOIC ACID RECEPTOR GAMMA; SUPEROXIDE DISMUTASE; TOCILIZUMAB; TOLL LIKE RECEPTOR 2; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG;

AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; ASSESSMENT OF HUMANS; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; FUNCTIONAL RATING SCALE; HUMAN; IMMUNOASSAY; INFLAMMATION; PERIPHERAL BLOOD MONONUCLEAR CELL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION;

EID: 84980052306     PISSN: None     EISSN: 2165591X     Source Type: Journal    
DOI: None     Document Type: Article

References (22)

1. Henkel JS, Engelhardt JI, Siklos L, Simpson EP, Kim SH, Pan T, Goodman JC, Siddique T, Beers DR and Appel SH. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol 2004; 55: 221-235.
2. Graves MC, Fiala M, Dinglasan LA, Liu NQ, Sayre J, Chiappelli F, van Kooten C and Vinters HV. Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells. Amyotroph Lateral Scler Other Motor Neuron Disord 2004; 5: 213-219.
3. Fiala M, Chattopadhay M, La Cava A, Tse E, Liu G, Lourenco E, Eskin A, Liu PT, Magpantay L, Tse S, Mahanian M, Weitzman R, Tong J, Nguyen C, Cho T, Koo P, Sayre J, Martinez-Maza O, Rosenthal MJ and Wiedau-Pazos M. IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients. J Neuroinflammation 2010; 7: 76-90.
4. Liu G, Fiala M, Mizwicki MT, Sayre J, Magpantay L, Siani A, Mahanian M, Chattopadhyay M, La Cava A and Wiedau-Pazos M. Neuronal phagocytosis by inflammatory macrophages in ALS spinal cord: inhibition of inflammation by resolvin D1. Am J Neurodegener Dis 2012; 1: 60- 74.
5. Meissner F, Molawi K and Zychlinsky A. Mutant superoxide dismutase 1-induced IL-1beta accelerates ALS pathogenesis. Proc Natl Acad Sci U S A 2010; 107: 13046-13050.
6. Butovsky O, Siddiqui S, Gabriely G, Lanser AJ, Dake B, Murugaiyan G, Doykan CE, Wu PM, Gali RR, Iyer LK, Lawson R, Berry J, Krichevsky AM, Cudkowicz ME and Weiner HL. Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest 2012
7. Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S, Liao B and Appel SH. Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 2011; 134: 1293-1314.
8. Korn T, Bettelli E, Oukka M and Kuchroo VK. IL- 17 and Th17 Cells. Annu Rev Immunol 2009; 27: 485-517.
9. Miossec P, Korn T and Kuchroo VK. Interleukin- 17 and type 17 helper T cells. N Engl J Med 2009; 361: 888-898.
10. Scheller J, Chalaris A, Schmidt-Arras D and Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011; 1813: 878-888.
11. Kallen KJ, zum Buschenfelde KH and Rose- John S. The therapeutic potential of interleukin- 6 hyperagonists and antagonists. Expert Opin Investig Drugs 1997; 6: 237-266.
12. Nowell MA, Williams AS, Carty SA, Scheller J, Hayes AJ, Jones GW, Richards PJ, Slinn S, Ernst M, Jenkins BJ, Topley N, Rose-John S and Jones SA. Therapeutic targeting of IL-6 trans signaling counteracts STAT3 control of experimental inflammatory arthritis. J Immunol 2009; 182: 613-622.
13. Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J and Herrmann N. A meta-analysis of cytokines in Alzheimer's disease. Biol Psychiatry 2010; 68: 930-941.
14. Blum-Degen D, Muller T, Kuhn W, Gerlach M, Przuntek H and Riederer P. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci Lett 1995; 202: 17-20.
15. Hampel H, Sunderland T, Kotter HU, Schneider C, Teipel SJ, Padberg F, Dukoff R, Levy J and Moller HJ. Decreased soluble interleukin-6 receptor in cerebrospinal fluid of patients with Alzheimer's disease. Brain Res 1998; 780: 356 -359.
16. Marz P, Heese K, Hock C, Golombowski S, Muller-Spahn F, Rose-John S and Otten U. Interleukin- 6 (IL-6) and soluble forms of IL-6 receptors are not altered in cerebrospinal fluid of Alzheimer's disease patients. Neurosci Lett 1997; 239: 29-32.
17. Garbers C, Thaiss W, Jones GW, Waetzig GH, Lorenzen I, Guilhot F, Lissilaa R, Ferlin WG, Grotzinger J, Jones SA, Rose-John S and Scheller J. Inhibition of classic signaling is a novel function of soluble glycoprotein 130 (sgp130), which is controlled by the ratio of interleukin 6 and soluble interleukin 6 receptor. J Biol Chem 2011; 286: 42959-42970.
18. Nishimoto N, Ito K and Takagi N. Safety and efficacy profiles of tocilizumab monotherapy in Japanese patients with rheumatoid arthritis: meta-analysis of six initial trials and five longterm extensions. Mod Rheumatol 2010; 20: 222-232.
19. Ash Z and Emery P. The role of tocilizumab in the management of rheumatoid arthritis. Expert Opin Biol Ther 2012; 12: 1277-1289.
20. Schiff MH, Kremer JM, Jahreis A, Vernon E, Isaacs JD and van Vollenhoven RF. Integrated safety in tocilizumab clinical trials. Arthritis Res Ther 2011; 13: R141.
21. Murakami M and Nishimoto N. The value of blocking IL-6 outside of rheumatoid arthritis: current perspective. Curr Opin Rheumatol 2011; 23: 273-277.
22. Waetzig GH and Rose-John S. Hitting a complex target: an update on interleukin-6 transsignalling. Expert Opin Ther Targets 2012; 16: 225-236.