Suppression of the development of experimental allergic encephalomyelitis by suramin

Veen, Roel C. van der; Asghar, Syed S.; Uitdehaag, B. M. J.; Helm, H J van der; Hommes, O.R.

doi:10.1016/0028-3908(85)90206-0

Cited by 12 publications

(2 citation statements)

References 10 publications

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“…Alternatively, DSG may inhibit invasion of activated T cells into the target organ by suppressing enzymes involved in transendothelial migration, while leaving adhesion molecules (CD2, ICAM-1, LFA-1) on T cells unaffected, as in our experiments. For example, heparin or suramin, agents inhibiting cell migration by suppression of T cell-or tumour cell-derived heparanase [41,42], have been successfully used to suppress EAE (42,43], encephalogenicity of MBP-specific T cells, or allograft rejection [44]. The hypothesis that DSG could interfere with homing and trafficking of activated T cells by suppressing enzymes involved in T cell migration may be strengthened by the observation that DSG significantly suppressed activity of some lymphocyte-related enzymes [45].…”

Section: Discussionmentioning

confidence: 99%

Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat

Jung

Toyka

Hartung

1994

Clinical and Experimental Immunology

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SUMMARYThe influence of the immunosuppressivc antibiotic agent 15-deoxyspergualin (DSG) on macrophages and autoreactive T helper lymphocytes from Lewis rats was analysed in vitro and in vivo. DSG did not inhibit antigen-or mitogen-induced proliferation of encephalitogenic or neuritogenic T helper cell lines in vitro. However, the presence of DSG during in vitro activation of the T cells strongly suppressed or completely abrogated their capacity to induce encephalitis (EAE) or neuritis (EAN) after adoptive transfer to naive rats, although expression of activation markers or adhesion molecules on the T line blasts was not down-regulated by DSG, Like activationinduced T cell proliferation, IL-2-dependent growth of CD4^ T line cells was not affected by DSG, Preincubation of CD4^ T line cells in DSG during IL-2-driven proliferation for 48 h, however, inhibited the subsequent antigen-but not mitogen-induced activation of these T cells, although neither density of T eel) receptors nor other surface molecules involved in antigen recognition were lowered on the cells exposed to DSG. Similar to its effect in vitro, in vivo administration of DSG for 10 days even at a concentration with cumulative toxicity did not suppress in vitro proliferation of spleen cells induced by mitogen or a mitogenic combination of anti-CD2 antibodies. Furthermore, spleen cell and peripheral blood lymphocyte (PBL) surface antigens, particularly MHC molecules, were not altered by long-term treatment with DSG for 30 days. While there was a slight reduction in the number of polymorphonuclear cells in both populations, the proportion of the different leucocyte subpopulations remained unchanged. In contrast to the strong functional impact of DSG on autoreactive T helper cells, the drug did not inhibit the oxidative burst of macrophages or their MHC antigen expression. This study demonstrates a clear inhibitory effect of DSG on CD4''' T lymphocytes, but not macrophages. It provides an explanation for recent observations of a strong immunosuppressive in vivo effect of DSG on transplantation rejection and experimental autoimmune diseases, despite a normal mitogen response of T cells exposed to DSG in vivo and in vitro.

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Section: Discussionmentioning

confidence: 99%

Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat

Jung

Toyka

Hartung

1994

Clinical and Experimental Immunology

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“…These observations have been recently reviewed by Asghar [4] and Patrick and Johnson [5]. More recently, suppression of development of EAE and suppression of hu man vasculitis by the complement inhibitors suramin [6] and chlorpromazine [7], respec tively, has been shown. Here we show that certain low molecular weight complement in hibitors, namely suramin [8][9][10][11][12], 2-hydroxystilbamidine [13,14], chlorpromazine [15] and chlorophenothiazine sulphonate [ 16] can strongly suppress complement-mediated vas cular injury seen in the Arthus reaction.…”

Section: Introductionmentioning

confidence: 92%

Suppression of Complement-Mediated Vascular Injury at Arthus Reaction Sites by Complement Inhibitors

Ss¹,

Kp²,

Kammeijer³

et al. 1986

Complement

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Certain complement inhibitors, namely chlorpromazine, suramin, 2-hydroxystilbamidine and chlorophenothiazine sulphonate were tested for their ability to suppress complement deposition and vascular injury at the site of an Arthus reaction. Deposition of complement was suppressed in the order 2-hydroxystilbamidine > suramin > chlorpromazine. All the above mentioned four compounds strongly protected vascular injury as observed by electron microscopic studies. At Arthus reaction sites prepared without drug treatment venules ranged from normal to severely altered and damaged. Discontinuities in endothelial linings varied from small to longer stretches. In the latter situation remaining endothelial cells were degenerated and endothelial remnants did not have an intact basal lamina. After treatment with the above complement inhibitors, at arthus reaction sites some venules appeared normal, whereas others were altered but in all cases the endothelium and its basal lamina remained intact.

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Suramin inhibits the mixed lymphocyte reaction by suppressing lymphokine production

1992

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New compounds with a greater potency than cyclosporin A (CyA) for thwarting host rejection of organ transplantation are being sought. Suramin sodium may be a novel drug to prevent or delay graft rejection and graft-vs-host disease (GVHD), because of its in vitro and in vivo immunosuppressive properties. Since the allogeneic mixed lymphocyte reaction (MLR) is considered to be the in vitro counterpart of the initial T-lymphocyte recognition and response to allogeneic histocompatibility antigens on grafted tissue or organ and to GVHD, we initially evaluated the in vitro suppressive effect of suramin in the allogeneic MLR. Suramin inhibited the H-2- and HLA-incompatible MLR in a dose-dependent manner. The suppressive effect was observed both in the primary and in the secondary MLR. The suppression of the MLR by suramin is due predominantly to the inhibition of interleukin-2 (IL-2) production by the responding T cells.

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Suppression of the development of experimental allergic encephalomyelitis by suramin

Cited by 12 publications

References 10 publications

Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat

Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat

Suppression of Complement-Mediated Vascular Injury at Arthus Reaction Sites by Complement Inhibitors

Suramin inhibits the mixed lymphocyte reaction by suppressing lymphokine production

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