Mechanism and Clinical Significance of IL-6 Combined with TNF-ÃÂ± or IL-1 for the Induction of Acute Phase Proteins SAA and CRP in Chronic Inflammatory Diseases
Soken-Nakazawa J Song and Kazuyuki Yoshizaki*
Division of Biological and Molecular Science, Department of Organic Fine Chemicals, The Institute of Scientific and Industrial Research, Osaka University, Japan
- Corresponding Author:
- Kazuyuki Yoshizaki
Division of Biological and Molecular Science
Department of Organic Fine Chemicals
The Institute of Scientific and Industrial Research
Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
E-mail: [email protected]
Received date: March 17, 2016; Accepted date: May 03, 2016; Published date: May 09, 2016
Citation: Song SNJ, Yoshizaki K (2016) Mechanism and Clinical Significance of IL-6 Combined with TNF-α or IL-1 for the Induction of Acute Phase Proteins SAA and CRP in Chronic Inflammatory Diseases. J Alcohol Drug Depend 4:239. doi:10.4172/2329-6488.1000239
Copyright: © 2016 Song SNJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Serum amyloid A (SAA) and C-reactive protein (CRP) are two major acute phase proteins whose serum concentrations increase in response to inflammation, though the exact mechanism underlying this induction remains unknown. Dysregulated production of interleukin (IL)-6 plays a pathogenic role in various inflammatory diseases such as rheumatoid arthritis, Castleman’s disease and systemic juvenile idiopathic arthritis. IL-6 blocking therapy with an anti-IL-6 receptor antibody (tocilizumab) can ameliorate clinical symptoms and abnormal laboratory findings, and completely normalize CRP and SAA levels in rheumatoid arthritis patients. Conversely, therapy for blocking tumor necrosis factor (TNF)-α, another key pathogenic factor in rheumatoid arthritis, barely lowers CRP and SAA to within their normal range, suggesting that IL-6 and TNF-α play different roles in the induction of acute phase protein expression. To clarify the different pathogenic roles and mechanisms of IL-6 and TNF-α or IL-1 in the induction of CRP and SAA in chronic inflammatory diseases, we investigated the transcriptional regulation mechanisms of SAA and CRP using hepatoma-derived cell lines in vitro, and related these mechanisms to the different effects of IL-6 and TNF-α blocking therapies on serum SAA and CRP in rheumatoid arthritis patients in vivo. We propose transcriptional regulation models for inflammatory cytokine-induced SAA and CRP expression that explain why IL-6 plays an essential role in the induction of SAA and CRP in the presence of inflammation.