AB0037 Characterising Multiple Molecule-Modulating Response of TNF-Alpha and Interleukin-6 by Combination of Methotrexate and Aconite in Interferon Gamma-Induced Toxicity Setting. (15th July 2016)

• Record Type: Journal Article
• Authors: Oh, D.-S.; Park, G.; Choi, S.
• Is Part Of: Annals of the rheumatic diseases. Volume 75(2016)Supplement 2
• Page Start: 909
• Page End: 910
• Publication Date: 2016-07-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2016-eular.5401
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: TNF-alpha (TNF-α) and interleukin-6 (IL-6) are one of the molecules which have been the targets of interest in rheumatoid arthritis (RA). Among the therapeutic strategies, simultaneous modulation of the two is regarded as providing the stability on the networks of the relevant molecules and sufficient profile for multi-therapeutic targets. Objectives: To characterise multiple molecule-modulating profile of TNF-α and IL-6, we experimented the anti-inflammatory phenotypes of the two by adopting well-known therapeutic, methotrexate (MTX) and newly recognised herbal, aconite ( Aconitum carmichaelii ) in the setting of interferon-gamma-induced inflammatory toxicity in macrophage. Methods: Mouse macrophage Raw264.7 cells were treated with MTX (0.01–1 mM) and processed aconite (Aconibal®, 0.01–1 mg/mL). The levels of TNF-α and IL-6 were measured by spectrophotometre (VersaMax ELISA, Molecular devices, USA), then, as a parametric approach, median and dose effect were analysed to calculate the combination index (CI) and standard isobologramme were presented using CalcuSyn software (CalcuSyn 2.0, Biosoft, UK). Results: Anti-inflammatory phenotypes of TNF-α and IL-6 level were shown in aconite dose-dependent manner. The doses of 0.75 mg/mL of aconite and 0.25 mM of MTX indicated the lowest CI as 0.272 for TNF-α and 7916 for IL-6, which was sparing effect compared with single treat by 3.9 mM and 0.6 mM of MTX, respectively. Reflecting the response, TNF-α was modulated with the synergistic profiles in normalised isobologramme. Conclusions: Stable modulation of TNF-α and IL-6 and synergistic response on TNF-α were characterised. Further approaches on network stability of the relevant molecules are needed. References: Zhao W, Yang H. Statistical Methods in Drug Combination Studies. CRC Press 2015 ISBN 978–1-4822–1674–5. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010 Jan 15;70(2):440–6. Detert J, Klaus P. Biologic monotherapy in the treatment of rheumatoid arthritis. Biologics 2015;9:35–43. Park G, Kim KM, Choi S, Oh DS. Aconitum carmichaelii protects against acetaminophen-induced hepatotoxicity via B-cell lymphoma-2 protein-mediated inhibition of mitochondrial dysfunction. Environ Toxicol Pharmacol in press doi:10.1016/j.etap.2016.01.012 Acknowledgement: The study was funded by Korea Institute of Oriental Medicine (KIOM) which grant number was K16253. Disclosure of Interest: None declared