Seluang Fish (Rasbora sp.) Oil Improves Interleukin-17 Levels and Disease Activity in Rheumatoid Arthritis

Radiyati Umi Partan, Rodry Mikhael, Triawan Adinata, Surya Darma, Muhammad Reagan, Rina Kriswiastiny, Yulianto Kusnadi, Eddy Mart Salim


BACKGROUND: Vitamin D has a role in downregulating the proinflammatory cytokines as well as promoting the antiinflammatory pathway in rheumatoid arthritis (RA). Seluang fish (Rasbora sp.) has potency as a new source of vitamin D. Previous study had proven Seluang fish oil efficacy in systemic lupus erythematosus. However, there are no trials that prove its efficacy in RA yet. Hence, this study was conducted to find out the ability of Seluang fish oil to improve proinflammatory cytokines, vitamin D levels, and disease activity in RA.

METHODS: A clinical trial with a randomized and double-blind method was done in two groups, each one consisting of 17 RA subjects. One group was given 500 mL of a Seluang fish oil capsule (contains 665 IU cholecalciferol), while the other group was given a placebo daily, for 12 consecutive weeks. Measurements of the RA disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR) and DAS28 C-reactive protein (DAS28-CRP), as well as measurement of interleukin (IL)-6, IL-17, and vitamin D levels by using immunoassay method were performed before and after the supplementation.

RESULTS: Significant alterations in the lower levels of IL-17 were observed in the Seluang fish oil group (p=0.031), but not in the placebo group (p=0.320). Reduction of DAS28-ESR (p=0.000) and DAS28-CRP (p=0.000) score demonstrated that the Seluang fish oil supplementation was useful in reducing RA disease activity. No significant shift was observed in either vitamin D (p=0.967) or IL-6 levels (p=0.076) after Seluang Fish Oil supplementation.

CONCLUSION: Seluang fish oil is effective in lowering IL-17 levels, DAS28-ESR, and DAS28-CRP, but not in improving vitamin D level or lowering IL-6 level in RA patients.

KEYWORDS: rheumatoid arthritis, seluang fish oil, interleukin-6, interleukin-17, vitamin D, DAS28

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Hidayat R, Suryana BPP, Wijaya LK, Ariane A, Hellmi RY, Adnan E, et al. Indonesian Rheumatology Association (IRA) recommendations for diagnosis and management of rheumatoid arthritis. Indones J Rheumatol. 2021; 13(1): 322–443, CrossRef.

Gary S Firestein. Etiology and pathogenesis of rheumatoid arthritis. In: Gary S Firestein, Budd RC, Gabrial SE, McInnes IB OJ, editor. Kelley and Firestein Texbook of Rheumatology. 10th ed. Philadelphia: Elsevier; 2017. p. 1115–66, CrossRef.

Gaber W, Azkalany GS, Gheita TA, Mohey A, Sabry R. Clinical significance of serum interleukin-6 and -174 G/C promoter polymorphism in rheumatoid arthritis patients. Egypt Rheumatol. 2013; 35(2): 107–13, CrossRef.

Nedal N, Magda E, Wafaa Y, Badrrawia, El-bussiouni S, Akef A, et al. T helper 17 cells and interleukin-17 in patients in rheumatoid arthritis. Int J Clin Rheumatol. 2019; 14(3): 113–9, article.

Meena N, Chawla SPS, Garg R, Batta A, Kaur S. Assessment of Vitamin D in rheumatoid arthritis and its correlation with disease activity. J Nat Sci Biol Med. 2018; 9(1): 54–8, CrossRef.

Wulandari D, Barlianto W, Sari TL. Low level of vitamin D is correlated with high C-reactive protein (CRP) and disease activity in Indonesian Juvenile Idiopathic Arthritis (JIA) patients. Indones Biomed J. 2020; 12(2): 149–56, CrossRef.

Penserga EG, Partan RU, Hidayat R, Saputra N, Prapto H, Rahmayani F. Seluang (Rasbora agrotyenia) fish oil increases vitamin D in autoimmune patients (systemic lupus erythematosus). J Phys Conf Ser. 2019; 1246: 012036, CrossRef.

Guan Y, Hao Y, Guan Y, Bu H, Wang H. The effect of vitamin D supplementation on rheumatoid arthritis patients: a systematic review and meta-analysis. Front Med (Lausanne). 2020; 7: 596007, CrossRef.

Franco AS, Freitas TQ, Bernardo WM, Pereira RMR. Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases. Medicine. 2017; 96(23): e7024, CrossRef.

Kim H, Baek S, Hong SM, Lee J, Jung SM, Lee J, et al. 1,25-dihydroxy vitamin D3 and interleukin-6 blockade synergistically regulate rheumatoid arthritis by suppressing interleukin-17 production and osteoclastogenesis. J Korean Med Sci. 2020; 35(6): 1–10, CrossRef.

Sun X, Li R, Cai Y, Al-Herz A, Lahiri M, Choudhury MR, et al. Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region. Lancet Reg Health West Pac. 2021; 15: 100240, CrossRef.

Kanjana K, Chevaisrakul P, Matangkasombut P, Paisooksantivatana K, Lumjiaktase P. Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis. Sci Rep. 2020; 10: 19789, CrossRef.

Suryani FY, Setyawati TR, Yanti AH. Struktur populasi ikan seluang (Rasbora argyrotaenia) di hilir sungai sekadau kecamatan sekadau hilir kabupaten sekadau. Protobiont. 2019; 8(2): 74–81, CrossRef.

Partan RU, Hidayat R. The potential role of seluang fish oil (Rasbora Spp) in improving calcium, zinc and vitamin D3 deficiencies. Int J Oceans Oceanogr. 2017; 11(2): 285–91, article.

Partan RU, Hidayat R. Exploration of seluang fish (Rasbora argyrotaenia) oil extraction methods by enzyme extraction and wet pressing with quality analysis. AACL Bioflux. 2020; 13(4): 2283–9, article.

Partan RU, Hidayat R, Saputra N, Rahmayani F, Prapto H, Yudha TW. Seluang fish (Rasbora Spp.) oil decreases inflammatory cytokines via increasing vitamin D level in systemic lupus erythematosus. Open Access Maced J Med Sci. 2019; 7(9): 1418–21, CrossRef.

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010; 62(9): 2569–81, CrossRef.

Fraenkel L, Bathon JM, England BR, St.Clair EW, Arayssi T, Carandang K, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2021; 73(7): 924–39, CrossRef.

Partan RU, Hidayat R, Lusiana E. The efficacy of seluang fish (Rasbora argyrotaenia) oil in cognitive function and expression of brain-derived neurotrophic factor (BDNF) in rattus norvegicus strain Wistar. Res J Pharm Biol Chem Sci. 9(5): 1581–6, article.

Sukharani N, Dev K, Rahul F, Bai P, Ali A, Avinash F, et al. Association between rheumatoid arthritis and serum vitamin D levels. Cureus. 2021; 13(9): e18255, CrossRef.

Pinzon R, Wijaya VO, Paramitha D. Vitamin D status and cognitive performance of post stroke patients. Mol Cell Biomed Sci. 2021; 5(1): 22–6, CrossRef.

Monica E, Hasanah PD, Fadillah A, Aulia R, Sulistijono E, Wibowo S. Administration of vitamin D3 improves hemoglobin level by regulating TNF-a and IL-6 in DSS-induced colitis mice. Indones Biomed J. 2020; 12(2): 130–5, CrossRef.

El-Banna HS, Gado SE. Vitamin D: does it help Tregs in active rheumatoid arthritis patients. Exp Rev Clin Immunol. 2020; 16(8): 847–53, CrossRef.

Abiola TS, David OO, Olatunde FE. Effect of tannin-rich extract of chasmanthera dependens on piroxicam-induced liver damage in male wistar rats. Mol Cell Biomed Sci. 2021; 5(1): 2–36, CrossRef.

Gopal K, Thevarajah M, Ng CM, Raja J. Effects of vitamin D on disease activity and serum interleukin-6 in rheumatoid arthritis. Int J Rheum Dis. 2019; 22(5): 834–41, CrossRef.

Ruliani H, Kalim H, Putra Suryana B, Handono K, Rematologi dan Imunologi Bagian Ilmu Penyakit Dalam Rumah Sakit Umum Saiful Anwar Malang D. Correlation of vitamin D, TNF-α, and clinical manifestation in rheumatoid arthritis patients. Jurnal Kedokteran Brawijaya. 2014; 28(1): 30–4, CrossRef.

Alpízar-Rodríguez D, Pluchino N, Canny G, Gabay C, Finckh A. The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology. 2017; 56(8): 1254–63, CrossRef.

Salim EM, Partan RU, Hidayat R. Betok fish (Anabas testudineus) oil decreases inlammatory cytokine through increasing vitamin D level in rats-induced systemic lupus erythematosus. Open Acess Maced J Med Sci. 2020; 8(A): 234–8, CrossRef.

Pludowski P, Takacs I, Boyanov M, Belaya Z, Diaconu CC, Mokhort T, et al. Clinical practice in the prevention, diagnosis and treatment of vitamin D deficiency: a Central and Eastern European Expert Consensus Statement. Nutrients. 2022; 14(7): 1483, CrossRef.

Aslam MM, John P, Bhatti A, Jahangir S, Kamboh MI. Vitamin D as a principal factor in mediating rheumatoid arthritis-derived immune response. Biomed Res Int. 2019; 2019: 3494937, CrossRef.

Berlanga-Taylor AJ, Plant K, Dahl A, Lau E, Hill M, Sims D, et al. Genomic response to vitamin D supplementation in the setting of a randomized, placebo-controlled trial. EBioMedicine. 2018; 31: 133–42, CrossRef.

Yegorov S, Bromage S, Boldbaatar N, Ganmaa D. Effects of vitamin D supplementation and seasonality on circulating cytokines in adolescents: analysis of data from a feasibility trial in Mongolia. Front Nutr. 2019; 6: 166, CrossRef.

Barahona Correa JE, Franco Cortés MA, Ángel Uribe J, Rodríguez Camacho LS. Comparison of plasma cytokine levels before and after treatment with rituximab in patients with rheumatoid arthritis and systemic lupus erythematosus-associated polyautoimmunity. Universitas Médica. 2018; 59(3): 1–16, CrossRef.

Naghavi Gargari B, Behmanesh M, Shirvani Farsani Z, Pahlevan Kakhki M, Azimi AR. Vitamin D supplementation up-regulates IL-6 and IL-17A gene expression in multiple sclerosis patients. Int Immunopharmacol. 2015; 28(1): 414–9, CrossRef.

Prtina A, Simović NR, Milivojac T, Vujnić M, Grabež M, Djuric D, et al. The effect of three-month Vitamin D supplementation on the levels of homocysteine metabolism markers and inflammatory cytokines in sera of psoriatic patients. Biomolecules. 2021; 11(12): 1865, CrossRef.

Wahono CS, Saveria I, Setyorini CD, Wahyuni ZD, Kalim H, Handono K. Effects of vitamin D3 (cholecalciferol) supplementation on systemic lupus erythematosus patients with hypovitaminosis D on serum pro-inflammatory cytokines (IL-6, IL-7, IFN-Gamma), anti-inflammatory cytokine (TGF-Beta) and anti-ds DNA levels. Indones J Rheumatol. 2021; 12(2): 302–8, CrossRef.

Toghianifar N, Ashtari F, Zarkesh-Esfahani SH, Mansourian M. Effect of high dose vitamin D intake on interleukin-17 levels in multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial. J Neuroimmunol. 2015; 285: 125–8, CrossRef.

Brożyna AA, Kim TK, Zabłocka M, Jóźwicki W, Yue J, Tuckey RC, et al. Association among vitamin D, retinoic acid-related orphan receptors, and vitamin d hydroxyderivatives in ovarian cancer. Nutrients. 2020; 12(11): 3541, CrossRef.


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