Original Article

Acta Pharmacologica Sinica (2006) 27, 1071–1077; doi:10.1111/j.1745-7254.2006.00322.x


Curcumin regulated shift from Th1 to Th2 in trinitrobenzene sulphonic acid-induced chronic colitis

Ming Zhang3, Chang-sheng Deng1, Jia-ju Zheng2 and Jian Xia1

  1. 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
  2. 2Municipal Hospital of Suzhou, Suzhou 215008, China
  3. 3Department of Gastroenterology, Drum Tower Hospital of Nanjing, Nanjing 210008, China

Correspondence: Dr Ming Zhang, E-mail: ming_zhang0923@hotmail.com

Received 9 October 2005; Accepted 6 February 2006.





To investigate the therapeutic effects of curcumin (Cur) on trinitrobenzene sulphonic acid (TNBS)-induced colitis and the effects of Cur on the balance of Th1/Th2 cytokines.



Colitis was induced by TNBS and treated with Cur (30 mgdotkg-1dotd-1, ip), dexamethasone (Dex, 2 mgdotkg-1dotd-1), or Cur plus dexamethasone (Cur+Dex, 30 mgdotkg-1dotd-1 Cur ip+2 mgdotkg-1dotd-1 Dex, ip). mRNA in colon mucosa were detected by realdottime quantitative polymerase chain reaction. Intracellular cytokines were detected by flow cytometry and concentrations of cytokines in sera were detected by enzymedotlinked immunosorbent analysis.



Both Cur and Dex improved body weight loss, ameliorated histological images and decreased macroscopic score and myeloperoxidase activity. Cur decreased the expression of Th1 cytokines (IL-12, IFN-gamma, TNF-alpha, IL-1) and increased the expression of Th2 cytokines (IL-4 and IL-10) in colon mucosa. Cur also increased the proportion of IFN-gamma/IL-4 in splenocytes and circulation. Dex and Cur+Dex decreased the expression of Th1 cytokines but could not increase the expression of Th2 cytokines and the proportion of IFN-gamma/IL-4.



Cur exerted therapeutic effects on colitis by regulating the shift from Th1 to Th2.


colitis, curcumin, IL-4, IL-12, Th1, Th2



  1. Ammon HPT, Wahl MA. Pharmacology of curcuma longa. Planta Med 1991; 57: 1–7. | Article | PubMed | ISI | ChemPort |
  2. Kang BY, Song YJ, Kim KM, Choe YK, Hwang SY, Kim TS. Curcumin inhibits Th1 cytokine profile in CD4+ T cells by suppressing interleukin-12 production in macrophages. Br J Pharmacol 1999; 128: 380–4. | Article | PubMed | ChemPort |
  3. Kang BY, Chung SW, Chung W, Im S, Hwang SY, Kim TS. Inhibition of interleukin-12 production in lipopolysaccharide-activated macrophages by curcumin. Eur J Pharmacol 1999; 19: 191–5. | Article |
  4. Kobayashi T, Hashimoto S, Horie T. Curcumin inhibition of dermatophagoides farinea-induced interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GM-CSF) production by lymphocytes from bronchial asthmatics. Biochem Pharmacol 1997; 54: 819–24. | Article | PubMed | ChemPort |
  5. Schmidt C, Stallmach A. Etiology and pathogenesis of inflammatory bowel disease. Minerva Gastroenterol Dietol 2005; 51: 127–45. | PubMed | ChemPort |
  6. Elson CO, Sartor RB, Tennyson GS, Riddell RH. Experimental models of inflammatory bowel disease. Gastroenterology 1995; 109: 1344–67. | Article | PubMed | ISI | ChemPort |
  7. Elson CO, Beagley KW, Sharmanov AT, Fujihashi K, Kiyono H, Tennyson GS, et al. Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. J Immunol 1996; 157: 2174–85. | PubMed | ChemPort |
  8. Tozawa K, Hanai H, Sugimoto K, Baba S, Sugimura H, Aoshi T, et al. Evidence for the critical role of interleukin-12 but not interferon-gamma in the pathogenesis of experimental colitis in mice. J Gastroenterol Hepatol 2003; 18: 578–87. | Article | PubMed | ChemPort |
  9. Salh B, Assi K, Templeman V, Parhar K, Owen D, Gomez-Munoz A, et al. Curcumin attenuates DNB-induced murine colitis. Am J Physiol Gastrointest Liver Physiol 2003; 285: G235–43. | PubMed | ChemPort |
  10. Sugimoto K, Hanai H, Tozawa K, Aoshi T, Uchijima M, Nagata T, et al. Curcumin prevents and ameliorates trinitrobenzene sulfonic acid-induced colitis in mice. Gastroenterology 2002; 123: 1912–22. | Article | PubMed | ChemPort |
  11. Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das PK. Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. Br J Pharmacol 2003; 139: 209–18. | Article | PubMed | ISI | ChemPort |
  12. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989; 96: 795–803. | PubMed | ISI | ChemPort |
  13. Maisel A, Cesario D, Baird S, Rehman J, Haghighi P, Carter S. Experimental autoimmune myocarditis produced by adoptive transfer of splenocytes after myocardial infarction. Circ Res 1998; 82: 458–63. | PubMed | ChemPort |
  14. Egi H, Hayamizu K, Yoshimitsu M, Shimamoto F, Oishi K, Ohmori I, et al. Regulation of T helper type-1 immunity in hapten-induced colitis by host pretreatment with granulocyte colony-stimulating factor. Cytokine 2003; 23: 23–30. | Article | PubMed | ChemPort |
  15. Colon AL, Menchen LA, Hurtado O, de Cristobal J, Lizasoain I, Leza JC, et al. Implication of TNF-alpha convertase (TACE/ADAM 17) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis. Cytokine 2001; 16: 220–6. | Article | PubMed | ChemPort |
  16. Caspi RR. IL-12 in autoimmunity. Clin Immunol Immunopathol 1998; 88: 4–13. | Article | PubMed | ISI | ChemPort |
  17. Chandramohan N, John JB. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through janus kinase-STAT pathway in T lymphocytes. J Immunol 2002; 169: 6506–13.
  18. DeKruyff RH, Fang Y, Umetsu DT. Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol 1998; 160: 2231–7. | PubMed | ChemPort |
  19. Cao W, Chen Y, Alkan S, Subramaniam A, Long F, Liu H, et al. Human T helper (Th) cell lineage commitment is not directly linked to the secretion of IFN-gamma or IL-4: characterization of Th cells isolated by FACS based on IFN-gamma and IL-4 secretion. Eur J Immunol 2005; 35: 2709–17. | Article | PubMed | ChemPort |
  20. Xie QM, Chen JQ, Shen WH, Bian RL. Correlative changes of interferon-gamma and interleukin-4 between cortical layer and pulmonary airway of sensitized rats. Acta Pharmacol Sin 2002; 23: 248–52. | PubMed | ChemPort |
  21. Sarah GH, Josue P, Laura K, Denise R, Richard PP. Prostaglandins as modulators of immunity. Trends Immunol 2002; 23: 144–50. | Article | PubMed | ISI | ChemPort |
  22. Pereira MA, Grubbs CJ, Barnes LH, Li H, Olson GR, Eto I, et al. Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a] anthracene-induced mammary cancer in rats. Carcinogenesis 1996; 17: 1305–11. | Article | PubMed | ISI | ChemPort |
  23. Plummer SM, Holloway KA, Manson MM, Munks RJ, Kaptein A, Farrow S, et al. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 1999; 18: 6013–20. | Article | PubMed | ISI | ChemPort |
  24. Elenkov IJ. Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad Sci 2004; 1024: 138–46. | Article | PubMed | ChemPort |