Immunosuppressive Effect of Cyclosporin A in Two Lymphocyte Transfer Models in Rats: Comparison of in Vivo and in Vitro Treatment

Ryffel, Bernhard; Feurer, Camille; Heuberger, Barbara; Borel, J. F.

doi:10.1016/s0171-2985(82)80061-2

Cited by 18 publications

(5 citation statements)

References 16 publications

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“…The dose of CsA employed in our study was effective in inhibiting both alloantibody and cellular immunity responses in various models in the rat 27–30 . Our data are similar to those reported previously regarding the effect of CsA in single‐allergen exposure of sensitized BN rats, 24,25 where no inhibition of allergen‐induced BHR by CsA was detected, although there was a significant reduction in eosinophils, CD4 + T cells and CD8 + T cells in the airways submucosa 24 .…”

Section: Discussionsupporting

confidence: 90%

Effects of cyclosporin A and a rapamycin derivative (SAR943) on chronic allergic inflammation in sensitized rats

Eynott¹,

Salmon²,

Huang³

et al. 2003

Immunology

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SUMMARYImmunomodulators such as cyclosporin A (CsA) and SAR943 (32-deoxorapamycin) inhibit single allergen-induced allergic in¯ammation such as eosinophilic and lymphocytic in®ltration and mRNA expression for interleukin (IL)-4 and IL-5. We examined the effects of CsA and SAR943, administered orally, on asthmatic responses in a rat model of chronic allergic in¯amma-tion. Sensitized Brown-Norway (BN) rats were exposed to ovalbumin (OVA) aerosol every third day on six occasions. CsA (5 mg/kg/day), SAR943 (2Á5 mg/kg/day) or vehicle (Neoral TM ) was administered orally, once a day, from days 10 to 21 (a total of 12 doses). We measured eosinophilic and T-cell in¯ammation in the airways, proliferation of airway cells by incorporation of bromodeoxyuridine (BrdU) and bronchial responsiveness to acetylcholine. CsA had no effects, while SAR943 inhibited airway smooth muscle (ASM, P < 0Á05) and epithelial cell (P < 0Á01) BrdU incorporation, and the number of CD4T cells (P < 0Á05), without effects on BHR. ASM thickness was not signi®cantly increased following chronic allergen exposure. Therefore, CsA and SAR943 have no effect on chronic eosinophilic in¯ammation, while SAR943, but not CsA, had a small effect on the proliferation of ASM and epithelium.

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Section: Discussionsupporting

confidence: 90%

Effects of cyclosporin A and a rapamycin derivative (SAR943) on chronic allergic inflammation in sensitized rats

Eynott¹,

Salmon²,

Huang³

et al. 2003

Immunology

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“…These studies explore further the somewhat unexpected and enigmatic finding (18) that when irradiated, marrow-reconstituted rats are given daily maintenance doses for 6 wk of CSA, a drug usually used to suppress alloreactivity and some autoimmune conditions (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), they develop an acute, usually fatal, autoimmune syndrome soon after the drug is discontinued . We report here several findings concerning the onset of the CSA-induced autoimmunity .…”

Section: Discussionmentioning

confidence: 98%

Cyclosporine-induced autoimmunity. Conditions for expressing disease, requirement for intact thymus, and potency estimates of autoimmune lymphocytes in drug-treated rats.

Sorokin¹,

Kimura²,

Schröder³

et al. 1986

The Journal of Experimental Medicine

110

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These studies explore the phenomenon of cyclosporine-induced autoimmunity in irradiated Lewis rats. We show that (a) the presence of a thymus is required, and autoimmune precursors develop in and exit from this organ to the peripheral lymphocyte pool within a 2-wk period after the initiation of cyclosporine treatment; (b) adoptive transfers of drug-induced autoimmunity to irradiated secondary recipients can be accomplished with relatively few cells of the Th subset, and these transfers of autoimmunity can be blocked by cotransfer of normal lymphoid cells; and (c) potency estimates, using popliteal lymph node assays in syngeneic and F1 recipients indicate similar levels of auto- and alloreactivity by cells from drug-induced autoimmune donors. These various findings indicate that this particular animal model may be useful for studies of the onset and control of autoimmunity, and they raise the possibility that the lack of autoimmunity in normal animals and its induction with cyclosporine may involve similar cellular mechanism as have been found to be operative in GVH reactions and specifically induced immunologic resistance to GVHD.

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“…However, in a model such as experimental autoimmune uveitis, treatment with CS-A starting only during the effector phase proved to be successful (24). Moreover, therapeutic treatment with CS-A demonstrated a pronounced reduction of the inflammatory symptoms in adjuvant arthritis (8) and an impressive improvement of the conditon of experimental allergic encephalomyelitis in the rat (25).…”

Section: Discussionmentioning

confidence: 99%

Paradoxical effects of cyclosporin A on collagen arthritis in rats.

Kaibara¹,

Hotokebuchi²,

Takagishi³

et al. 1983

The Journal of Experimental Medicine

121

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The effect of the immunosuppressive agent cyclosporin A (CS-A) on collagen arthritis in Sprague-Dawley rats is investigated. A 14-d course of CS-A treatment at doses of 15 mg/kg per day or more, begun on the same day as type II collagen immunization, suppressed the development of arthritis as well as humoral and delayed-type hypersensitivity (DTH) skin test responses to type II collagen, possibly by interfering with helper T cells. Additional studies demonstrated that CS-A treatment only during the induction phase of immunity proved to be successful. When CS-A treatment was started only during the immediately preclinical phase of arthritis or after the disease onset, a significant enhancement of the disease was obtained in a dose-dependent manner. This enhancement was accompanied by an augmentation of DTH skin reactions, while antibody responses were either suppressed or unaffected. These results appear to be attributable at least in part to a suppressive effect of CS-A on a population of suppressor T cells, thus resulting in a T cell-mediated helper effect. It is therefore reasonable to assume that the paradoxical effects of CS-A on collagen arthritis in rats might be caused by an altering of the sensitive balance of the two regulatory subpopulations of T cells. It is also possible that cell-mediated immune responses may play an important role in influencing the course of the disease.

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Immunosuppressive Effect of Cyclosporin A in Two Lymphocyte Transfer Models in Rats: Comparison of in Vivo and in Vitro Treatment

Cited by 18 publications

References 16 publications

Effects of cyclosporin A and a rapamycin derivative (SAR943) on chronic allergic inflammation in sensitized rats

Effects of cyclosporin A and a rapamycin derivative (SAR943) on chronic allergic inflammation in sensitized rats

Cyclosporine-induced autoimmunity. Conditions for expressing disease, requirement for intact thymus, and potency estimates of autoimmune lymphocytes in drug-treated rats.

Paradoxical effects of cyclosporin A on collagen arthritis in rats.

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