Skip Navigation
Skip to contents

KMJ : Kosin Medical Journal

OPEN ACCESS
SEARCH
Search

Articles

Page Path
HOME > Kosin Med J > Volume 30(1); 2015 > Article
Original Article
Effects of L-ascorbic acid on the production of pro-inflammatory and anti-inflammatory cytokines in C57BL/6 mouse splenocytes
Eun Hee Kong1, Sun Young Ma2, Jee Yeong Jeong3, Kwang Hyuk Kim4
Kosin Medical Journal 2015;30(1):41-49.
DOI: https://doi.org/10.7180/kmj.2015.30.1.41
Published online: January 20, 2015

1Department of Family Medicine, Kosin University College of Medicine, Busan, Korea

2Department of Radiation oncology, Kosin University College of Medicine, Busan, Korea

3Department of Biochemistry, Kosin University College of Medicine, Busan, Korea

4Department of Microbiology, Kosin University College of Medicine, Busan, Korea

Corresponding Author:Jee yeong Jeong, Department of Biochemistry, Kosin University College of Medicine 262, Gamcheon-ro, Seo-gu, Busan, South Korea (602-703) TEL: +82-51-990-6365 FAX: +82-51-990-3045 E-mail: fmeunhee@gmail.com
• Received: December 27, 2013   • Accepted: July 9, 2014

Copyright © 2015 Kosin University School of Medicine Proceedings

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • 1,527 Views
  • 15 Download
  • 16 Crossref
  • Objective
    The imbalance between pro-inflammatory and anti-inflammatory cytokines may underlie different pain states. Although ascorbic acid is the most important physiological antioxidant that affects host defense mechanisms and immune homeostasis, there is limited information on the effects of ascorbic acid on the production of cytokines.
  • Methods
    In this study, we investigated the in vitro effect of L-ascorbic acid (AA) on the production of pro-inflammatory and anti-inflammatory cytokines by stimulating C57BL/6 mouse splenocytes with the polyclonal activators lipopolysaccharide or concanavalin A.
  • Results
    AA significantly downregulated the expression of IL-6, IL-12, and TNF-α at 48 h and 72 h in mouse splenocytes treated with a combination of polyclonal activators and AA. AA treatment also resulted in upregulation of IL-4 and IL-10 at 72 h. These findings demonstrated that AA significantly potentiated production of anti-inflammatory cytokines whereas there was an inverse association between AA and expression of pro-inflammatory cytokines in mouse splenocytes.
  • Conclusion
    AA may have potential applications in the reduction of inflammatory pain because of its function in modulating the production of cytokines. However, further in vivo investigations are necessary to elucidate the mechanisms involved.
Fig. 1.
Effects of L-ascorbic acid on the production of pro-inflammatory cytokines in mouse splenocytes
kmj-30-41f1.jpg
Fig. 2.
Effects of L-ascorbic acid on the production of anti-inflammatory cytokines in mouse splenocytes
kmj-30-41f2.jpg
  • 1. Verri WA Jr, Cunha TM, Parada CA, Poole S, Cunha FQ, Ferreira SH. Hypernociceptive role of cytokines and chemokines: targets for analgesic drug development? Pharmacol Ther 2006;112:116–38.ArticlePubMed
  • 2. Chen Y, Boettger MK, Reif A, Schmitt A, Uçeyler N, Sommer C. Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice. Mol Pain 2010;6:13.ArticlePubMedPMC
  • 3. Kelley DS, Bendich A. Essential nutrients and immunologic functions. Am J Clin Nutr 1996;63:994S–6S.ArticlePubMed
  • 4. Puertollano MA, Puertollano E, de Cienfuegos GA, de Pablo MA. Dietary antioxidants: immunity and host defense. Curr Top Med Chem 2011;11:1752–66.ArticlePubMed
  • 5. Chambial S, Dwivedi S, Shukla KK, John PJ, Sharma P. Vitamin C in Disease Prevention and Cure: An Overview. Indian J Clin Biochem 2013;28:314–28.ArticlePubMedPMC
  • 6. Nam-Sung Kang, Suhkneung Pyo, eun-Hua sohn. In vitro Effects of L-Ascorbic Acid and Acrylamide on Lymphocyte Proliferation in Young and Aged Mice. J Food Sci Nutr 2010;15:19–23.Article
  • 7. Pae M, Ren Z, Meydani M, Shang F, Smith D, Meydani SN, et al. Dietary supplementation with high dose of epigallocatechin-3-gallate promotes inflammatory response in mice. J Nutr Biochem 2012;23:526–31.ArticlePubMed
  • 8. Cavaillon JM, Fitting C, Haeffner-Cavaillon N, Kirsch SJ, Warren HS. Cytokine response by monocytes and macrophages to free and lipoprotein-bound lipopolysaccharide. Infect Immun 1990;58:2375–82.ArticlePubMedPMC
  • 9. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A 2008;105:11105–9.ArticlePubMedPMC
  • 10. Moens B, Decanine D, Khouri R, Lopez G, Talledo M, Gotuzzo E, et al. Ascorbic acid has superior antiviral and antiproliferative effects over IFN-alpha in HAM/TSP PBMC ex vivo. Retrovirology 2011;8:A61.ArticlePMC
  • 11. Üçeyler N, Sommer C. Cytokine-induced pain: basic science and clinical implications. Rev Analg 2007;9:87–103.Article
  • 12. Kress M. Nociceptor Sensitization by Proinflammatory Cytokines And Chemokines. The Open Pain Journal 2010;3:97–107.Article
  • 13. Uceyler N, Sommer C. Cytokine regulation in animal models of neuropathic pain and in human diseases. Neurosci Lett 2008;437:194–8.ArticlePubMed
  • 14. Chen H, Karne RJ, Hall G, Campia U, Panza JA, Cannon RO 3rd, et al. High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance. Am J Physiol Heart Circ Physiol 2006;290:H137–45.ArticlePubMed
  • 15. Tousoulis D, Antoniades C, Vasiliadou C, Kourt-ellaris P, Koniari K, Marinou K, et al. Effects of atorvastatin and vitamin C on forearm hyperaemic blood flow, asymmentrical dimethylarginine levels and the inflammatory process in patients with type 2 diabetes mellitus. Heart 2007;93:244–6.ArticlePubMed
  • 16. Schafers M, Svensson CI, Sommer C, Sorkin LS. Tumor necrosis factor-alpha induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons. J Neurosci 2003;23:2517–21.ArticlePubMedPMC
  • 17. Zelenka M, Schafers M, Sommer C. Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain. Pain 2005;116:257–63.PubMed
  • 18. Cunha TM, Verri WA Jr, Valerio DA, Guerrero AT, Nogueira LG, Vieira SM, et al. Role of cytokines in mediating mechanical hypernociception in a model of delayed-type hypersensitivity in mice. Eur J Pain 2008;12:1059–68.ArticlePubMed
  • 19. Barksby HE, Lea SR, Preshaw PM, Taylor JJ. The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders. Clin Exp Immunol 2007;149:217–25.ArticlePubMedPMC
  • 20. Qiu J, Cafferty WB, McMahon SB, Thompson SW. Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. J Neurosci 2005;25:1645–53.ArticlePubMedPMC
  • 21. Cafferty WB, Gardiner NJ, Das P, Qiu J, McMahon SB, Thompson SW. Conditioning injury-induced spinal axon regeneration fails in interleukin-6 knockout mice. J Neurosci 2004;24:4432–43.ArticlePubMedPMC
  • 22. Gardiner NJ, Cafferty WB, Slack SE, Thompson SW. Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury. J Neurochem 2002;83:100–9.ArticlePubMed
  • 23. Obreja O, Biasio W, Andratsch M, Lips KS, Rathee PK, Ludwig A, et al. Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons. Brain 2005;128:1634–41.ArticlePubMed
  • 24. Juttler E, Tarabin V, Schwaninger M. Interleukin-6 (IL-6): a possible neuromodulator induced by neuronal activity. Neuroscientist 2002;8:268–75.ArticlePubMed
  • 25. Vollmer-Conna U, Fazou C, Cameron B, Li H, Brennan C, Luck L, et al. Production of proinflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans. Psychol Med 2004;34:1289–97.ArticlePubMed
  • 26. Wang XS, Shi Q, Williams LA, Cleeland CS, Mobley GM, Reuben JM, et al. Serum interleukin-6 predicts the development of multiple symptoms at nadir of allogeneic hematopoietic stem cell transplantation. Cancer 2008;113:2102–9.ArticlePubMed
  • 27. Karam MC, Hamdan HG, Abi Chedid NA, Bodman-Smith KB, Baroody GM. Interleukin-10 reduces hyperalgesia and the level of Interleukin-1beta in BALB/c mice infected with Leishmania major with no major effect on the level of Interleukin-6. J Neuroimmunol 2007;183:43–9.PubMed
  • 28. Milligan ED, Langer SJ, Sloane EM, He L, Wieseler-Frank J, O'Connor K, et al. Controlling pathological pain by adenovirally driven spinal production of the antiinflammatory cytokine, interleukin-10. Eur J Neurosci 2005;21:2136–48.ArticlePubMed
  • 29. Uceyler N, Rogausch JP, Toyka KV, Sommer C. Differential expression of cytokines in painful and painless neuropathies. Neurology 2007;69:42–9.ArticlePubMed
  • 30. Uceyler N, Sommer C. Status of immune mediators in painful neuropathies. Curr Pain Headache Rep 2008;12:159–64.ArticlePubMed

Figure & Data

References

    Citations

    Citations to this article as recorded by  
    • Interleukin-8 and neutrophil extracellular traps in children with lupus nephritis and vitamin C deficiency
      Chanunya Santiworakul, Wilasinee Saisorn, Nuanpan Siripen, Asada Leelahavanichkul, Pornpimol Rianthavorn
      Pediatric Nephrology.2024; 39(4): 1135.     CrossRef
    • Antioxidant Activity, Stability in Aqueous Medium and Molecular Docking/Dynamics Study of 6-Amino- and N-Methyl-6-amino-L-ascorbic Acid
      Lara Saftić Martinović, Nada Birkic, Vedran Miletić, Roberto Antolović, Danijela Štanfel, Karlo Wittine
      International Journal of Molecular Sciences.2023; 24(2): 1410.     CrossRef
    • Anticancer Activity of Mineral-Supplemented Organically Cultivated Carrot on HT-29 Cells and Its Anti-Inflammatory Effect on Mice Splenocytes
      Yanni Pan, Yeon-Jun Lee, Sin-Il Sin, Seung-Hwan Park, Kun-Young Park
      Applied Sciences.2023; 13(16): 9209.     CrossRef
    • Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats
      Suzan A. Khodir, Manar A. Faried, Huda I. Abd-Elhafiz, Eman M. Sweed, Krzysztof Siemianowicz
      BioMed Research International.2022; 2022: 1.     CrossRef
    • Combination Treatment of Omega-3 Fatty Acids and Vitamin C Exhibited Promising Therapeutic Effect against Oxidative Impairment of the Liver in Methotrexate-Intoxicated Mice
      Mohammed Alorabi, Doha Saad Mohammed, Gomaa Mostafa-Hedeab, Suzy A. El-Sherbeni, Walaa A. Negm, Ali Ismail A. Mohammed, Hayder M. Al-kuraishy, Nani Nasreldin, Saqer S. Alotaibi, Bashir Lawal, Gaber El-Saber Batiha, Carlos Adam Conte-Junior, Valeria Pasciu
      BioMed Research International.2022; 2022: 1.     CrossRef
    • STAT3 inhibition decreases ATP-induced MUC8 gene expression in human airway epithelial cells
      Cheol Hong Kim, Kyoung Seob Song
      Kosin Medical Journal.2022; 37(2): 134.     CrossRef
    • Critical review on the immunomodulatory activities of carrot’s β-carotene and other bioactive compounds
      Gemala Anjani, Fitriyono Ayustaningwarno, Rafika Eviana
      Journal of Functional Foods.2022; 99: 105303.     CrossRef
    • Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid
      Agnieszka Gęgotek, Elżbieta Skrzydlewska
      Antioxidants.2022; 11(10): 1993.     CrossRef
    • The Effect of Ascorbic Acid on Interleukin-10 and Tumor Necrosis Factor-α Cytokines in Rattus norvegicus with Endometritis
      Muhammad Oky Prabudi, M. F. G. Siregar, I. P. A. Nasution, S. Ilyas
      Open Access Macedonian Journal of Medical Sciences.2021; 9(A): 798.     CrossRef
    • Effect of Ascorbic Acid on Differentiation, Secretome and Stemness of Stem Cells from Human Exfoliated Deciduous Tooth (SHEDs)
      Shilpa Bhandi, Ahmed Alkahtani, Mohammed Mashyakhy, Abdulaziz S. Abumelha, Nassreen Hassan Mohammad Albar, Apathsakayan Renugalakshmi, Mazen F. Alkahtany, Ali Robaian, Asma Saleh Almeslet, Vikrant R. Patil, Saranya Varadarajan, Thodur Madapusi Balaji, Rod
      Journal of Personalized Medicine.2021; 11(7): 589.     CrossRef
    • Development of a novel in vitro insulin resistance model in primary human tenocytes for diabetic tendinopathy research
      Hui Yee Tan, Sik Loo Tan, Seow Hui Teo, Margaret M. Roebuck, Simon P. Frostick, Tunku Kamarul
      PeerJ.2020; 8: e8740.     CrossRef
    • Active Cousinia thomsonii Extracts Modulate Expression of Crucial Proinflammatory Mediators/Cytokines and NFκB Cascade in Lipopolysaccharide-Induced Albino Wistar Rat Model


      Khalid Bashir Dar, Ishfaq Shafi Khan, Shajrul Amin, Aijaz Hassan Ganie, Aashiq Hussain Bhat, Showkat Ahmad Dar, Bilal Ahmad Reshi, Showkat Ahmad Ganie
      Journal of Inflammation Research.2020; Volume 13: 829.     CrossRef
    • The potential cytoprotective effect of Vitamin C and Vitamin E on monosodium glutamate-induced testicular toxicity in rats
      Safaa Mohamed El Kotb, Dalia El-sayed El-ghazouly, Omnia Ameen
      Alexandria Journal of Medicine.2020; 56(1): 134.     CrossRef
    • Combination of ascorbic acid and calcitriol attenuates chronic asthma disease by reductions in oxidative stress and inflammation
      Farzaneh Kianian, Seyed Morteza Karimian, Mehri Kadkhodaee, Nasrin Takzaree, Behjat Seifi, Soheila Adeli, Elham Harati, Hamid Reza Sadeghipour
      Respiratory Physiology & Neurobiology.2019; 270: 103265.     CrossRef
    • Evaluation of Ascorbic Acid or Curcumin Formulated in a Solid Dispersion on Salmonella Enteritidis Infection and Intestinal Integrity in Broiler Chickens
      Daniel Hernandez-Patlan, Bruno Solis-Cruz, Karine P. Pontin, Juan D. Latorre, Xochitl Hernandez-Velasco, Ruben Merino-Guzman, Abraham Mendez-Albores, Billy M. Hargis, Raquel Lopez-Arellano, Guillermo Tellez-Isaias
      Pathogens.2019; 8(4): 229.     CrossRef
    • Amelioration of Escherichia coli‐induced endometritis with ascorbic acid in non‐pregnant mouse models
      Enitome Evi Bafor, Ikechukwu Onwukpa, Anne Oghenekevwe Itemire, Osemelomen Omoruyi, Ejiroghene Eferoba‐Idio, Kevin Odega, Osas Jim Eghianruwa
      American Journal of Reproductive Immunology.2018;[Epub]     CrossRef

    • PubReader PubReader
    • ePub LinkePub Link
    • Cite
      CITE
      export Copy
      Close
    • Download Citation
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

      Format:
      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      Include:
      • Citation for the content below
      Effects of L-ascorbic acid on the production of pro-inflammatory and anti-inflammatory cytokines in C57BL/6 mouse splenocytes
      Kosin Med J. 2015;30(1):41-49.   Published online January 20, 2015
      Close
    • XML DownloadXML Download
    Figure

    KMJ : Kosin Medical Journal