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Anti-cytokine Agents to Combat Oxidative Stress

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Studies on Arthritis and Joint Disorders

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Abstract

Oxidative stress induced by reactive oxygen species (ROS) is a key underlying mechanism of destructive and proliferative synovitis in rheumatoid arthritis (RA). Abundant ROS have been detected in the synovial fluid of inflamed joints. ROS are also important mediators of cardiovascular degeneration. Patients with RA have a higher risk for cardiovascular events. Recent studies reported the significant suppression of ROS and oxidative stress in the serum of patients with RA by biologics targeting the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. Indeed, serum ROS levels in patients with RA treated with an IL-6-blocking drug are significantly suppressed. Therapy blocking IL-1 also suppresses oxidative stress-induced changes in tissues of patients with RA. Taken together, these findings suggest that anti-cytokine therapies may not only reduce joint damage but vascular degeneration in patients with RA. Given that recent reports have pointed to the beneficial effects of anti-cytokine agents on cardiovascular degeneration, the observed beneficial effects in RA may rely in part on the reduction of oxidative stress.

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Abbreviations

AGE:

Advanced glycation end products

CAVI:

Cardio-ankle vascular index

CFR:

Coronary flow reserve

CRP:

C-reactive protein

DMARDs:

Disease-modifying antirheumatic drugs

ET:

Endothelin

FMD:

Flow-mediated dilatation

FN:

Interferon

IL:

Interleukin

LDL:

Low-density lipoprotein

MMP:

Matrix metalloproteinases

MMR:

Mismatch repair

mtDNA:

Mitochondrial DNA

MTX:

Methotrexate

NAC:

N-acetylcysteine

NO:

Nitric oxide

O2 − :

Superoxide

OA:

Osteoarthritis

·HO:

Hydroxyl radicals

ONOO− :

Peroxynitrite

RA:

Rheumatoid arthritis

RNS:

Reactive nitrogen species

ROM:

Reactive oxygen metabolites

ROS:

Reactive oxygen species

TNF:

Tumor necrosis factor

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Author information

Authors and Affiliations

  1. Department of Orthopaedics, National Hospital Organization, Osaka-Minami Medical Center, Osaka, Japan

    Makoto Hirao M.D., Ph.D.

  2. Department of Immune Disease Center, National Hospital Organization, Osaka-Minami Medical Center, Osaka, Japan

    Jun Hashimoto M.D., Ph.D.

  3. Department of Molecular Regulation for Intractable Diseases, Institute of Medical Science, Tokyo Medical University, Osaka Rheumatology Clinic, Tatsuno-Shinsaibashi Bld. 5th Floor, 4-4-10, Minamisenba, Chuo-ku, Osaka, 542-0081, Japan

    Norihiro Nishimoto M.D., Ph.D.

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  1. Makoto Hirao M.D., Ph.D.
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  2. Jun Hashimoto M.D., Ph.D.
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Correspondence to Norihiro Nishimoto M.D., Ph.D. .

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Editors and Affiliations

  1. Fac Farmacia, Department of Pharmacology, University of Valencia, Av Vicent Andres Estelles S/n Burjasot, Valencia, 46100, Spain

    Maria Jose Alcaraz

  2. , NEIRID Lab, Santiago University Clinical Hospital, Trav. Choupana sn, Santiago de Compostela, 15706, Spain

    Oreste Gualillo

  3. Fundación Jiménez Díaz Hospital, Rheumatology Division, Autonoma University, Avda Reyes Católicos 2, Madrid, 28040, Spain

    Olga Sánchez-Pernaute

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Hirao, M., Hashimoto, J., Nishimoto, N. (2013). Anti-cytokine Agents to Combat Oxidative Stress. In: Alcaraz, M., Gualillo, O., Sánchez-Pernaute, O. (eds) Studies on Arthritis and Joint Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-6166-1_16

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