DOI QR코드

DOI QR Code

The inhibitory effects of Gami-Phedoc-San on TNF-α, IL-1β and IFN-γ secretion from human monocytes

  • Kim Mi-Sun (Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University) ;
  • Lee Eun-Hee (Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University) ;
  • Choung Se-Young (College of Pharmacy, Kyunghee University)
  • Published : 2002.02.01

Abstract

In our study, the several cytokines were determined in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Adamantiades-Behcets patients. Adamantiades-Behcets disease (ABD) is a systemic inflammatory disorder and might involve immune dysfunction. High levels of $TNF-\alpha,\;IL-1\beta$ and $IFN-{\gamma}$ indicate the activation of inflammatory reactions and immune system in ABD. Gami-Phedoc-San (GPS) is an Oriental herbal medication, which has been used in Korea for the treatment of ABD. GPS (1 mg/ ml) significantly inhibited the secretion of proinflammatory cytokines, $TNF-\alpha\;and\;IL-1\beta$, compared to absence of GPS (by $50.5{\pm}1.9%$ inhibition for $TNF-\alpha$ and $106.9{\pm}16.8%$ for $IL-1\beta$). GPS also inhibited the production of $IFN-\gamma$, immunoregulatory Th1 cytokine, by $78.4{\pm}2.8%$. The inhibitory effects of GPS on cytokine secretion showed dose-dependent manner, and the pre-treatment of 1 mg/ml GPS had better effects than immunosuppressive drug for treatment of ABD, cyclosporin A. Our results suggest that GPS treatment for ABD patients might have pharmacological activity of immune and inflammatory responses through the cytokine modulation.

Keywords

References

  1. al-Dalaan A, al-Sedairy S, al-Balaa S, al-Ianadi M, Elramahi K, Bahabri S, Siddiqui S. (1995) Enhanced interleukin 8 secretion in circulation of patients with Behcet' s disease. J. Rheumatol. 22, 904-907.
  2. Arbesfeld SJ, Kurban AK. (1988) Behcets disease. New perspectives on an enigmatic syndrome. J. Am. Acad. Dermatol. 19, 767-779. https://doi.org/10.1016/S0190-9622(88)70233-9
  3. Bacon TH, Ozbakir F, Elms CA, Denman AM. (1984) Interferon-gamma production by peripheral blood mononuclear cells from patients with Behcet's syndrome. Clin. Exp. Immunol. 57, 541-547.
  4. Bang D, Hur W, Lee ES, Lee S. (1995) Prognosis and clinical relevance of recurrent oral ulceration in Behcet's disease. J. Dermatol. 22, 926-929. https://doi.org/10.1111/j.1346-8138.1995.tb03947.x
  5. Bang DS. (1997) Treatment of Behcets disease. Yonsei Med. J. 38, 401-410. https://doi.org/10.3349/ymj.1997.38.6.401
  6. Bondeson J, Maini RN. (2001) Tumour necrosis factor as a therapeutic target in rheumatoid arthritis and other chronic inflammatory diseases: the clinical experience with infliximab (Remicade). Int. J. Clin. Pract. 55, 211-216.
  7. Calabrese L, Fleischer AB. (2000) Thalidomide: Current and potential clinical applications. Am. J. Med. 108, 487-495. https://doi.org/10.1016/S0002-9343(99)00408-8
  8. Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, Longo DL, Taub DD, Oppenheim JJ. (1996) Indentification of defensin-1, defensin-2, and CAP37/Azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophiIs. J. Biol. Chem. 271, 2935-2940. https://doi.org/10.1074/jbc.271.6.2935
  9. Emmi L, Salvati G, Brugnolo F, Marchione T. (1995) Immunopathological aspects of Behcet's disease. Clin. Exp. Rheumatol. 13, 687-691.
  10. Fujii N, Minagawa T, Nakane A, Kato F, Ohno S. (1983) Spontaneous production of gamma-interferon in cultures of T lymphocytes obtained from patients with Behcet's disease. J. Immunol. 130, 1683-1686.
  11. Hamzaoui K, Hamza M, Ayed K. (1990) Production of TNF-$\alpha$ and IL-1active Behcet's disease. J. Rheumatol. 17, 1428-1429.
  12. Hassard PV, Binder SW, Nelson V, Vasiliauskas EA. (2001) Anti-tumor necrosis factor monoclonal antibody therapy for gastrointestinal Behcet's disease: Case report. Gastroenterology 120, 995-999. https://doi.org/10.1053/gast.2001.22556
  13. Kaklamani VG, Vaiopoulos G, Kaklamanis PG. (1998) Behcet's disease. Semin. Arthritis. Rheum. 27, 197-217. https://doi.org/10.1016/S0049-0172(98)80001-2
  14. Kastner DL. (1997) Intermittent and periodic arthritic syndromes. In: Koopman WJ, editors. Arthritis and allied conditions: a textbook of rheumatology. 13th ed. Vol. 1. Baltimore: Williams & Wilkins, 1279-306.
  15. Katayama T, Tachinami K, Ishiguro M, Kubota Y. (1994) The relation between Behcets disease and interleukin-1$\beta$ production. Nippon Ganka Gakkai Zasshi. 98, 197-201.
  16. Katsantonis J, Adler Y, Orfanos CE, Zouboulis CC. (2000) Adamantiades-Behcets disease: serum IL-8 is a more reliable marker for disease activity than C-reactive protein and erythrocyte sedimentation rate. Dermatol. 201, 37-39. https://doi.org/10.1159/000018426
  17. Kim HM, Lee YM. (1999) Role of TGF-$\beta$1 on the IgE-dependent anaphylaxis reaction. J. Immunol. 162, 4960-4965.
  18. Kotake S, Higashi K, Yoshikawa K, Sasamoto Y, Okamoto T, Matsuda H. (1999) Central nervous system symptoms in patients with Behcet disease receiving cyclosporin therapy. Ophthalmology 106, 586-589. https://doi.org/10.1016/S0161-6420(99)90120-3
  19. Masuda K, Nakajima A, Urayama A, Nakae K, Kogure M, Inaba G. (1989) Double-masked trial of cyclosporin versus colchcine and long-term open study of chclosporin in Behcets disease. Lancet 1, 1093-1096.
  20. McHugh SM, Rifkin IR, Deighton J, Wilson AB, Lachmann PJ, Lockwood CM, et aI. (1995) The immunosuppressive drug thalidomide induces T helper cell type 2 (Th2) and concomitantly inhibits Th1 cytokine production in mitogen- and antigen-stimulated human peripheral mononuclear cell cultures. Clin. Exp. Immunol. 99, 160-167. https://doi.org/10.1111/j.1365-2249.1995.tb05527.x
  21. Mege JL, Dilsen N, Sanguedolce V, Gul A, Bongrand P, Roux H, et al. (1993) Overproduction of monocyte derived tumor necrosis factor a, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behcets disease. A comparative study with familial Mediterranean fever and healthy subjects. J. Rheumatol. 20, 1544-1549.
  22. Nakae K, Masaki F, Hashimoto T, Inaba G, Mochizuki M, Sakane T. (1993) Recent epidemiological features of Behcet's disease in Japan. In: Wechsler B, Godeau P, editors. Behcet's disease. Amsterdam: Excerpta Media, 145-151.
  23. Nussenblatt RB. (1997) Uveitis in Behcet' s disease. Int. Rev. Immunol. 14, 67-79.
  24. Ozoran K, Aydintug O, Tokgoz G, Duzgun N, Tutkak H, Curler A. (1995) Serum levels of interleukin-8 in patients with Behcet's disease. Ann. Rheum. Dis. 54, 610. https://doi.org/10.1136/ard.54.7.610
  25. Ozyazgan Y, Yurdakul S, Yazici H, Tuzun B, Iscimen A, Tuzun Y, et al. (1992) Low dose cyclosporin A versus plused cyclophosphamide in Behcet's syndrom: a single masked trial. Br. J. Ophthalmol. 76, 241-243. https://doi.org/10.1136/bjo.76.4.241
  26. Poulter LW, Lehner T. (1989) Immunohistology of oral lesions from patients with resurrent oral ulcers and Behcet's syndrome. Clin. Exp. Immunol. 78, 189-95.
  27. Sakane T, Takeno M, Suzuki N, Inaba G. (1999) Behcet's disease. N. Engl. J. Med. 341, 1284-91. https://doi.org/10.1056/NEJM199910213411707
  28. Sakane T, Takeno M. (2000) Novel approaches to Behcet's disease. Exp. Opin. Invest. Drugs 9, 1993-2005. https://doi.org/10.1517/13543784.9.9.1993
  29. Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. (1991) Thalidomide selectively inhibits tumor necrosis factor a production by stimulated human monocytes. J. Exp. Med. 173, 699-703. https://doi.org/10.1084/jem.173.3.699
  30. Sayinalp N, Ozcebe Ol, Ozdemir a, Haznedaroglu IC, Dundar S, KirazliS. (1996) Cytokines in Behcets disease. J. Rheumatol. 23, 321-322.
  31. Taub DD, Anver M, Oppenheim JJ, Longo DL, Murphy WJ. (1996) TIymphocyte recruitment by interleukin-8 (IL-8). J. Clin. Invest. 97, 1931-1941. https://doi.org/10.1172/JCI118625
  32. Yamakawa Y, Sugita Y, Nagatani T, Takahashi S, Yamakawa T, Tanaka SI, Nakamura S, Ohno S, Sekihara H, Okuda K, Nakajima H. (1996) Interleukin-6 (IL-6) in patients with Behcet's disease. J. Dermatol. Sci. 11, 189-195. https://doi.org/10.1016/0923-1811(95)00439-4
  33. Yazici H, Yurdakul S, Hamuryudan V. (1999) Behcet's syndrome. Curr. Opin. Rheumatol. 11, 53-57. https://doi.org/10.1097/00002281-199901000-00009
  34. Yosipovitch G, Shohat B, Bshara J, Wysenbeek A, Weinberger A. (1995) Elevated serum interleukin 1 receptors and interleukin 1$\beta$ in patients with Behcet's disease: Correlations with disease activity and severity. Isr. J. Med. Sci. 31, 345-348.
  35. Zouboulis CC, Katsantonis J, Ketteler R, Treudler R, Kaklanmani E, Hornemann S, Kaklamanis P, Orfanos CE. (2000) Adamantiades-Behcet's disease: interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells. Arch. Dermatol. Res. 292, 279-284. https://doi.org/10.1007/s004030000128
  36. Zouboulis CC. (1999) Epidemiology of Adamantiades-Behcet's disease. Ann. Med. Interne. 150, 488-498.