Effects of deoxyspergualin on collagen arthritis in mice

Takagishi, Kenji; Yamamoto, Makoto; Maeda, Kenji; Nishimura, Akito; Yonemoto, Kohzoh; Hotokebuchi, Takao; Kaibara, N.

doi:10.1016/0090-1229(90)90171-l

Cited by 17 publications

(15 citation statements)

References 21 publications

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“…Similar results concerning the prophylactic effect of FK 506 in collagen arthritis have been obtained in mice using doses of drug 25 times lower than effective doses of CSA 46 . As with CsA, FK 506 was ineffective in treatment of established lesions in the mouse.…”

Section: Arthritissupporting

confidence: 73%

Fk 506 and Autoimmune Disease: Perspective and Prospects

Thomson

Starzl

1992

Autoimmunity

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Section: Arthritissupporting

confidence: 73%

Fk 506 and Autoimmune Disease: Perspective and Prospects

Thomson

Starzl

1992

Autoimmunity

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“…FK-506 significantly suppressed the DTH response at a dose of 5 mg/kg and decreased the anti-CII antibody titer at doses more than 3 mg/kg. In the mouse CIA model, FK-506 significantly suppressed both the DTH response and anti-CII antibody production at a dose of 3 mg/kg, but, at a dose of 2 mg/kg, this drug significantly suppressed anti-CII antibody production but not the DTH response when given prophylactically (19). In in vitro studies in mice, FK-506 suppressed mixed lympho cyte reactions, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as IL-2, IL-3 and interferon (IFN)-r, and the expression of IL-2 receptor at low concentrations (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the suppressive mechanism of mizoribine on rat CIA, as well as mouse CIA, is probably related to its suppression of cellular immunity. These drugs have been reported to have suppressive and/or therapeutic effects on mice and on other rat strains with CIA (9, 13, 19,[22][23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Immunopharmacological Studies on Collagen-Induced Arthritis in Dark Agouti (DA) Rats.

et al. 1997

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“…This dose is known to exert a marked suppressive effect on clinical signs of autoimmune reactions in vivo [8][9][10][11][12][13], Spleen cells from DSG-treated rats could be activated as strongly as spleen cells from sham-treated control rats by optimal and suboptimal concentrations of Con A and by stimulation via the alternative pathway using a mitogenic combination of two different anti-CD2 antibodies [35] (Fig. 5), This result indicates that mitogenic agents fail to demonstrate an elTect of DSG on T lymphocytes, which becomes apparent only during specific activation via the T cell receptor, A potential influence of DSG on lymphoid cells other than CD4" lymphocytes was screened by FACS analysis of PBL or spleen cells after treatment of naive rats for 30 or 32 consecutive days, respectively, with 5 mg/kg per day.…”

Section: In Vivo Apptication Of Dsg Does Not Affect Mitogenic Activatmentioning

confidence: 99%

“…The antibiotic and antitumour activities of DSG were discovered first [1,2], but its most promising effect is its immunosuppressive activity as shown in a variety of transplantation models [3 6] and after transplantation in man [7]. Furthermore, DSG prevented or ameliorated autoimmune disease in different experimental models [8][9][10][11][12][13], and its potential efficacy in treating multiple sclerosis is now being evaluated in a clinical trial.…”

Section: Introductionmentioning

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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Effects of deoxyspergualin on collagen arthritis in mice

Cited by 17 publications

References 21 publications

Fk 506 and Autoimmune Disease: Perspective and Prospects

Fk 506 and Autoimmune Disease: Perspective and Prospects

Immunopharmacological Studies on Collagen-Induced Arthritis in Dark Agouti (DA) Rats.

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

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