Effects of L-ascorbic acid on the production of pro-inflammatory and anti-inflammatory cytokines in C57BL/6 mouse splenocytes

다국어 초록 (Multilingual Abstract)

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.

참고문헌 (Reference)

1 Chambial S, "Vitamin C in Disease Prevention and Cure : An Overview" 28 : 314-328, 2013

2 Schafers M, "Tumor necrosis factor-alpha induces mechanical allodynia after spinal nerve ligation by activation of p38 MAPK in primary sensory neurons" 23 : 2517-2521, 2003

3 Barksby HE, "The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders" 149 : 217-225, 2007

4 Uceyler N, "Status of immune mediators in painful neuropathies" 12 : 159-164, 2008

5 Wang XS, "Serum interleukin-6predicts the development of multiple symptoms at nadir of allogeneic hematopoietic stem cell transplantation" 113 : 2102-2109, 2008

6 Cunha TM, "Role of cytokines in mediating mechanical hypernociception in a model of delayed-type hypersensitivity in mice" 12 : 1059-1068, 2008

7 Vollmer-Conna U, "Production of proinflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans" 34 : 1289-1297, 2004

8 Chen Q, "Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice" 105 : 11105-11109, 2008

9 Kress M, "Nociceptor Sensitization by Proinflammatory Cytokines And Chemokines" 3 : 97-107, 2010

10 Chen Y, "Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice" 6 : 13-, 2010

11 Zelenka M, "Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain" 116 : 257-263, 2005

12 Juttler E, "Interleukin-6(IL-6) : a possible neuromodulator induced by neuronal activity" 8 : 268-275, 2002

13 Karam MC, "Interleukin-10reduces 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" 183 : 43-49, 2007

14 Nam-Sung Kang, "In vitro Effects of L-Ascorbic Acid and Acrylamide on Lymphocyte Proliferation in Young and Aged Mice" 한국식품영양과학회 15 (15): 19-23, 2010

15 Verri WA Jr, "Hypernociceptive role of cytokines and chemokines: targets for analgesic drug development?" 112 : 116-138, 2006

16 Chen H, "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" 290 : H137-H145, 2006

17 Obreja O, "Fast modulation of heatactivated ionic current by proinflammatory interleukin 6 in rat sensory neurons" 128 : 1634-1641, 2005

18 Gardiner NJ, "Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones : regulation by nerve injury" 83 : 100-109, 2002

19 Kelley DS, "Essential nutrients and immunologic functions" 63 : 994S-996S, 1996

20 Tousoulis D, "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" 93 : 244-246, 2007

21 Uceyler N, "Differential expression of cytokines in painful and painless neuropathies" 69 : 42-49, 2007

22 Pae M, "Dietary supplementation with high dose of epigallocatechin-3-gallate promotes inflammatory response in mice" 23 : 526-531, 2012

23 Puertollano MA, "Dietary antioxidants : immunity and host defense" 11 : 1752-1766, 2011

24 Üçeyler N, "Cytokine-induced pain : basic science and clinical implications" 9 : 87-103, 2007

25 Cavaillon JM, "Cytokine response by monocytes and macrophages to free and lipoprotein-bound lipopolysaccharide" 58 : 2375-2382, 1990

26 Uceyler N, "Cytokine regulation in animal models of neuropathic pain and in human diseases" 437 : 194-198, 2008

27 Milligan ED, "Controlling pathological pain by adenovirally driven spinal production of the anti-inflammatory cytokine, interleukin-10" 21 : 2136-2148, 2005

28 Cafferty WB, "Conditioning injury-induced spinal axon regeneration fails in interleukin-6knock-out mice" 24 : 4432-4443, 2004

29 Qiu J, "Conditioning injury-induced spinal axon regener ation requires signal transducer and activator of transcription 3 activation" 25 : 1645-1653, 2005

30 Moens B, "Ascorbic acid has superior antiviral and antiproliferative effects over IFN-alpha in HAM/TSP PBMC ex vivo" 8 : A61-, 2011