{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T15:21:07Z","timestamp":1765639267127,"version":"3.48.0"},"reference-count":32,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1986,3]]},"abstract":"<jats:p>The in vitro effect of Cyclosporin A on the regulation of immunoglobulin production was investigated in 16 patients with primary biliary cirrhosis. A significant improvement in concanavalin A induced suppression of IgG and IgM producing cells was observed after prior incubation of mononuclear cells with 300 ng\/ml Cyclosporin A for 30 minutes. No effect was seen on spontaneous or pokeweed mitogen induced immunoglobulin production, nor on con A induced suppression if Cyclosporin A was added after 24 hours. Incubation of mononuclear cells with a variable dose of Cyclosporin A showed an effect only at 250-500 ng\/ml. Higher and lower doses had no effect. This dose dependent effect of Cyclosporin A is likely to be related to a differential inhibitory effect on T helper and T suppressor cells and may underlie the clinical benefit being observed in current clinical trials.<\/jats:p>","DOI":"10.1136\/gut.27.3.317","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"317-323","source":"Crossref","is-referenced-by-count":12,"title":["In vitro effect of cyclosporin A on immunoglobulin production and concanavalin A induced suppression in primary biliary cirrhosis."],"prefix":"10.1136","volume":"27","author":[{"given":"M N","family":"Al-Aghbar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G J","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K T","family":"Nouri-Aria","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Neuberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A L","family":"Eddleston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1986,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(79)92440-1","article-title":"Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases and 2 livers","volume":"2","author":"Calne, R.Y.; Rolles, K.; White, D.J.G.","year":"1979","unstructured":"Calne RY, Rolles K, White DJG et al. Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases and 2 livers. Lancet 1979; 2: 1033-6.","journal-title":"Lancet"},{"key":"ref_2","first-page":"281","article-title":"Liver transplantation 1980, with particular reference to","volume-title":"Cyclosporin A. Transplant Proc 1981; 13","author":"Starzl, T.E.; Iwatsuki, G.; Klintmalm, G.; Schroter, J.; Weil, R.; Koep, L.J.; Porter, K.A.","unstructured":"Starzl TE, Iwatsuki G, Klintmalm G, Schroter J, Weil R, Koep LJ, Porter KA. Liver transplantation 1980, with particular reference to Cyclosporin A. Transplant Proc 1981; 13: 281-5."},{"key":"ref_3","first-page":"486","article-title":"Cyclosporin improves Graves'","volume":"2","author":"Weetman, A.P.; Macgregor, A.M.; Ludgate, M.; Beck, L.; Mills, P.V.; Lazarus, J.H.; Hall, R.","year":"1983","unstructured":"Weetman AP, Macgregor AM, Ludgate M, Beck L, Mills PV, Lazarus JH, Hall R. Cyclosporin improves Graves' ophthalmolopathy. Lancet 1983; 2: 486-9.","journal-title":"ophthalmolopathy. Lancet"},{"key":"ref_4","first-page":"235","article-title":"Treatment of intraocular inflammatory disease with cyclosporin A","volume":"2","author":"Nussenblatt, R.B.; Palestine, A.G.; Rook, A.H.; Scher, I.; Wacker, W.B.; Gery, I.","year":"1983","unstructured":"Nussenblatt RB, Palestine AG, Rook AH, Scher I, Wacker WB, Gery I. Treatment of intraocular inflammatory disease with cyclosporin A. Lancet 1983; 2: 235-8.","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1126\/science.6367043","article-title":"Effects of cyclosporin in recent onset insulin dependent diabetes mellitus","volume":"223","author":"Stiller, C.; Dupre, J.; Gent, M.; Jenner, M.R.; Keown, P.A.; Laupacis, A.; Martell, R.; Rodger, N.W.; von Graffenried, B.; Wolfe, B.M.","year":"1984","unstructured":"Stiller C, Dupre J, Gent M, Jenner MR, Keown PA, Laupacis A, Martell R, Rodger NW, von Graffenried B, Wolfe BM. Effects of cyclosporin in recent onset insulin dependent diabetes mellitus. Science 1984; 223: 1362-7.","journal-title":"Science"},{"key":"ref_6","first-page":"1174","article-title":"Cyclosporin for pulmonary sarcoidosis","volume":"1","author":"Rebuck, A.S.; Stiller, C.R.; Braude, A.C.; Laupacis, A.; Cohen, R.D.; Chapman, K.R.","year":"1984","unstructured":"Rebuck AS, Stiller CR, Braude AC, Laupacis A, Cohen RD, Chapman KR. Cyclosporin for pulmonary sarcoidosis. Lancet 1984; 1: 1174.","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/S0140-6736(84)91358-8","article-title":"Cyclosporin for Crohn's disease","volume":"1","author":"Allison, M.C.; Pounder, R.E.","year":"1984","unstructured":"Allison MC, Pounder RE. Cyclosporin for Crohn's disease. Lancet 1984; 1: 902-3.","journal-title":"Lancet"},{"key":"ref_8","first-page":"1223","article-title":"Effects of cyclosporin A on suppressor and inducer T lymphocytes in primary biliary cirrhosis","volume":"2","year":"1981","unstructured":"Routhier G, Epstein 0, Janossy G, Thomas HC, Sherlock S. Effects of cyclosporin A on suppressor and inducer T lymphocytes in primary biliary cirrhosis. Lancet 1981; 2: 1223-6.","journal-title":"Lancet"},{"key":"ref_9","first-page":"74","article-title":"Correction of the suppressor cell defect of PBC by Cyclosporin A","volume":"4","author":"Alexander, G.J.M.; Al-Aghbar, M.N.A.; Neuberger, J.; Nouri-Aria, K.T.; Neuberger, J.; Eddleston, A.L.W.F.; Williams, R.","year":"1984","unstructured":"Alexander GJM, Al-Aghbar MNA, Neuberger J, Nouri-Aria KT, Neuberger J, Eddleston ALWF, Williams R. Correction of the suppressor cell defect of PBC by Cyclosporin A. [Abstract]. Liver 1984; 4: 74."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/0016-5085(80)90136-5","article-title":"Abnormal regulation of immunoglobulin synthesis in vitro in primary biliary cirrhosis","volume":"79","author":"James, S.P.; Elson, C.O.; Jones, E.A.; Strober, W.","year":"1980","unstructured":"James SP, Elson CO, Jones EA, Strober W. Abnormal regulation of immunoglobulin synthesis in vitro in primary biliary cirrhosis. Gastroenterology 1980; 79: 242-54.","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0002-9343(83)91170-1","article-title":"Genetic abnormalities of immunoregulation in primary biliary cirrhosis","volume":"75","author":"Miller, K.B.; Sepersky, R.A.; Brown, K.M.; Goldberg, M.J.; Kaplan, M.M.","year":"1983","unstructured":"Miller KB, Sepersky RA, Brown KM, Goldberg MJ, Kaplan MM. Genetic abnormalities of immunoregulation in primary biliary cirrhosis. Am J Med 1983; 75: 75-80.","journal-title":"Am J Med"},{"key":"ref_12","first-page":"626","article-title":"A classification of chronic hepatitis: Lancet 1968; 2","author":"J, De Groote; VJ, Desmet; P, Gedigk; G, Korb; H, Popper; H, Poulsen; P, Scheur; M, Schmid; H, Thaler; E, Uehlinger; N, Wepler","unstructured":"De Groote J, Desmet VJ, Gedigk P, Korb G, Popper H, Poulsen H, Scheur P, Schmid M, Thaler H, Uehlinger E, Wepler N. A classification of chronic hepatitis: Lancet 1968; 2: 626-9."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0090-1229(78)90010-7","article-title":"Lymphocyte subsets and integrated immune function in ageing humans","volume":"10","author":"Hallgren, H.M.; Kersey, J.H.; Dubey, D.P.; Yunis, E.S.","year":"1978","unstructured":"Hallgren HM, Kersey JH, Dubey DP, Yunis ES. Lymphocyte subsets and integrated immune function in ageing humans. Clin Immunol Immunopathol 1978; 10: 65-78.","journal-title":"Clin Immunol Immunopathol"},{"key":"ref_14","first-page":"55","volume":"27","author":"Nouri-Aria, K.T.; Donaldson, P.T.; Hegarty, J.E.; Eddleston","year":"1979","unstructured":"Nouri-Aria KT, Donaldson PT, Hegarty JE, Eddleston 1979; 27: 55a."},{"key":"ref_15","first-page":"432","article-title":"Effect of cyclosporin A on in vitro proliferative activity and immunoglobulin A on in vitro proliferative human lymphoid cell subpopulation. Clin Exp Immunol","volume":"43","author":"Paavonen, G.; Jarvelelamen, H.; Kontiainen, S.; Hayry, P.","year":"1981","unstructured":"Paavonen G, Jarvelelamen H, Kontiainen S, Hayry P. Effect of cyclosporin A on in vitro proliferative activity and immunoglobulin A on in vitro proliferative human lymphoid cell subpopulation. Clin Exp Immunol 1981; 43: 432-50."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.4049\/jimmunol.125.6.2526","article-title":"A on functional B cell subset in the mouse","volume":"125","year":"1980","unstructured":"A on functional B cell subset in the mouse. J Immunol 1980; 125: 2526-31.","journal-title":"J Immunol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1084\/jem.158.3.690","article-title":"Selective suppression of an early step in human B cell activation by Cyclosporin A","volume":"158","author":"Muragachi, A.; Butler, J.L.; Kerhl, J.H.; Falkoff, R.J.M.; Fauci, A.S.","year":"1983","unstructured":"Muragachi A, Butler JL, Kerhl JH, Falkoff RJM, Fauci AS. Selective suppression of an early step in human B cell activation by Cyclosporin A. J Exp Med 1983; 158: 690-702.","journal-title":"J Exp Med"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"176","DOI":"10.4049\/jimmunol.132.1.176","article-title":"Sequential requirements for cell cycle progression of resting human B cells following activation by anti-Ig","volume":"132","author":"Muragachi, A.; Kehrl, J.H.; Butler, J.L.; Fauci, A.S.","year":"1984","unstructured":"Muragachi A, Kehrl JH, Butler JL, Fauci AS. Sequential requirements for cell cycle progression of resting human B cells following activation by anti-Ig. J Immunol 1984; 132: 176-80.","journal-title":"J Immunol"},{"key":"ref_19","first-page":"2601","article-title":"Effect of cyclosporin A on human lymphocyte responses in vitro","volume":"124","author":"Hess, A.D.; Tutschka, P.J.","year":"1980","unstructured":"Hess AD, Tutschka PJ. Effect of cyclosporin A on human lymphocyte responses in vitro. J Immunol 1980; 124: 2601-8.","journal-title":"J Immunol"},{"key":"ref_20","first-page":"104","article-title":"Inhibition of in vitro human lymphocyte responses by cyclosporin A","volume":"7","author":"Hess, A.D.; Matyas, JR, Tutschka; P.J.","year":"1979","unstructured":"Hess AD, Matyas JR, Tutschka PJ. Inhibition of in vitro human lymphocyte responses by cyclosporin A. Exp Hematol 1979; 7: 104-9.","journal-title":"Exp Hematol"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4049\/jimmunol.127.1.89","article-title":"Suppressive effects in vitro and in vivo","volume":"127","author":"Borel, J.F.; Wiesinger, E.H.; Collins, K.H.; Hutchinson, I.F.; Tilney, N.L.; Mannick, J.A.","year":"1981","unstructured":"Borel JF, Wiesinger EH, Collins KH, Hutchinson IF, Tilney NL, Mannick JA. Suppressive effects in vitro and in vivo. J Immunol 1981; 127: 89-93.","journal-title":"J Immunol"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/0090-1229(83)90191-5","article-title":"Experimental erythrocyte auto-immunity prevented by suppressor T cells in mice treated with Cyclosporin A","volume":"28","author":"Cox, K.O.; Allison, A.C.; Samcewicz, B.","year":"1983","unstructured":"Cox KO, Allison AC, Samcewicz B. Experimental erythrocyte auto-immunity prevented by suppressor T cells in mice treated with Cyclosporin A. Clin Immunol Immunopathol 1983; 28: 90-95.","journal-title":"Clin Immunol Immunopathol"},{"key":"ref_23","first-page":"2828","article-title":"Cyclosporin A and dexamethasone suppress T cell responses by selectively acting at distinct sites of the triggering process","volume":"124","author":"Larsson, E.L.","year":"1980","unstructured":"Larsson EL. Cyclosporin A and dexamethasone suppress T cell responses by selectively acting at distinct sites of the triggering process. J Immunol 1980; 124: 2828-33.","journal-title":"J Immunol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/eji.1830110812","article-title":"Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 2","volume":"11","author":"Bunjes, D.; Hardt, C.; Rollinghoff, M.; Wagner, H.","year":"1981","unstructured":"Bunjes D, Hardt C, Rollinghoff M, Wagner H. Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 2. Europ J Immunol 1981; 11: 657-61.","journal-title":"Europ J Immunol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/290792a0","article-title":"Cyclosporin A blocks the receptors for HLA-DR antigens in T cells","volume":"209","author":"Palacios, R.; Moller, G.","year":"1981","unstructured":"Palacios R, Moller G. Cyclosporin A blocks the receptors for HLA-DR antigens in T cells. Nature (Lond) 1981; 209: 792-4.","journal-title":"Nature (Lond)"},{"key":"ref_26","first-page":"2737","article-title":"Cyclosporin A does not prevent expression of Tac antigen, a probable TCGF receptor molecule, on mitogen stimulated T cells","volume":"130","author":"Miyawaki, T.; Yachie, A.; Ohzeki, S.; Nagaoki, T.; Taniguchi, N.","year":"1983","unstructured":"Miyawaki T, Yachie A, Ohzeki S, Nagaoki T, Taniguchi N. Cyclosporin A does not prevent expression of Tac antigen, a probable TCGF receptor molecule, on mitogen stimulated T cells. J Immunol 1983; 130: 2737-42.","journal-title":"J Immunol"},{"key":"ref_27","first-page":"67","article-title":"Effects of cyclosporin A on human lymphocytes in culture","volume":"1","author":"Leoni, P.; Garcia, R.C.; Allison, A.C.","year":"1978","unstructured":"Leoni P, Garcia RC, Allison AC. Effects of cyclosporin A on human lymphocytes in culture. J Clin Lab Immunol 1978; 1: 67-72.","journal-title":"J Clin Lab Immunol"},{"key":"ref_28","first-page":"153","article-title":"Effects of cyclosporin A on the metabolism of unstimulated and mitogen-activated lymphocytes","volume":"49","author":"Kay, J.E.; Benzie, C.R.","year":"1983","unstructured":"Kay JE, Benzie CR. Effects of cyclosporin A on the metabolism of unstimulated and mitogen-activated lymphocytes. Immunology 1983; 49: 153-60.","journal-title":"Immunology"},{"article-title":"The action of cyclosporin A on human lymphocytes","author":"Kahan, B.D.; Kerman, R.H.; Agostino, G.; Legrue, Friedkman A.; S.J.","key":"ref_29","unstructured":"Kahan BD, Kerman RH, Agostino G, Friedkman A. Legrue SJ. The action of cyclosporin A on human lymphocytes. In: ed. White DG Cyclosporin A. Amsterdam: Elsevier, 1982: 281."},{"key":"ref_30","first-page":"970","article-title":"Effects of Cyclosporin A on suppressor cell function in vito and in vitro in primary biliary cirrhosis","volume":"24","author":"Al-Aghbar, M.N.A.; Alexander, G.J.M.; Neuberger, J.; Nouri-Aria, K.T.; Eddelston, A.L.W.F.; Williams, R.","year":"1983","unstructured":"Al-Aghbar MNA, Alexander GJM, Neuberger J, Nouri-Aria KT, Eddelston ALWF, Williams R. Effects of Cyclosporin A on suppressor cell function in vito and in vitro in primary biliary cirrhosis. [Abstract] Gut 1983; 24: A970.","journal-title":"[Abstract] Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0016-5085(55)80027-3","article-title":"Effect of steroid therapy on the clinical and laboratory features of primary biliary cirrhosis","volume":"28","author":"Carman, C.T.; Giansiracusa, J.E.","year":"1955","unstructured":"Carman CT, Giansiracusa JE. Effect of steroid therapy on the clinical and laboratory features of primary biliary cirrhosis. Gastroenterology 1955; 28: 193-215.","journal-title":"Gastroenterology"},{"key":"ref_32","first-page":"227","article-title":"The late results of a long-term treatment of primary biliary cirrhosis with corticosteroids","volume":"16","author":"Howat, H.T.; Ralston, A.S.; Varley, H.; Wilson, J.A.C.","year":"1966","unstructured":"Howat HT, Ralston AS, Varley H, Wilson JAC. The late results of a long-term treatment of primary biliary cirrhosis with corticosteroids. Rev Int Hepatol 1966; 16: 227-38.","journal-title":"Rev Int Hepatol"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.27.3.317","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T15:18:41Z","timestamp":1765639121000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.27.3.317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1986,3]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1986,3,1]]},"published-print":{"date-parts":[[1986,3]]}},"alternative-id":["10.1136\/gut.27.3.317"],"URL":"https:\/\/doi.org\/10.1136\/gut.27.3.317","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"subject":[],"published":{"date-parts":[[1986,3]]}}}