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J F Borel

Publications and source records attributed to J F Borel.

At least 37 records · Page 2Linked to original sources
PubMed1991

Suppressor cells of popliteal lymph node origin are involved in the in vivo and in vitro control of experimental allergic encephalomyelitis effector cells in the Lewis rat.

Lewis rats immunized in the hind footpads with total guinea pig spinal cord tissue in mycobacteria-enriched complete Freund's adjuvant develop chronic relapsing experimental allergic encephalomyelitis. It was previously shown that popliteal lymph node cells (LNC) isolated at the time of the first recovery (day 16) and transferred into naive syngeneic recipients protect from active induction of the disease. On the other hand, inguinal LNC taken at the onset of the disease (day 11) induce under similar conditions an acceleration of the appearance of the clinical symptoms. In this report, we show that the in vivo suppressive activity of popliteal LNC is associated with the absence of production of interleukin 2 in this compartment. The lack of production of this lymphokine and the suppressive activity can be detected only in the popliteal compartment and appear as early as day 11 after immunization. We show that this suppressive population displays in vitro inhibitory activity on the proliferative response of the disease effectors (inguinal LNC) to guinea pig myelin basic protein. This suppressive activity is not abrogated by addition of interleukin 2, suggesting that these suppressor cells do not inhibit the proliferation by absorption of the released lymphokine or by inhibition of its production.

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PubMed1991

Mechanism of action of cyclosporin A and rationale for use in nephrotic syndrome.

Cyclosporin A (CyA, Sandimmun) is the forerunner of a new generation of immunosuppressive drugs. It is highly effective in both antibody- and cell-mediated immunity and in inhibiting chronic inflammatory reactions. Cyclosporin A is, therefore, widely used to prevent rejection in clinical organ transplantation and appears to be very promising in the treatment of several autoimmune diseases. Cyclosporin A is not only effective when given at the time of sensitization (prevention of disease), but also when administered therapeutically during an immune response, such as during the active course of an autoimmune disease. The most important aspect of its immunosuppressive mechanism is the inhibition of lymphokine production secreted by activated T cells. The pharmacological effects of CyA are rapid in onset, dose-dependent and often quickly reversible when treatment is stopped.

Animals↗
PubMed1990

Mechanism of action and rationale for cyclosporin A in psoriasis.

Cyclosporin A (CyA) is the forerunner of a new generation of immunosuppressive drugs. It is highly effective in both antibody- and cell-mediated immunity and in inhibiting chronic inflammatory reactions. Cyclosporin A is, therefore, widely used to prevent rejection in clinical organ transplantation and appears to be very promising in the treatment of several autoimmune diseases, in particular psoriasis. Cyclosporin A is not only effective when given at the time of sensitization (prevention of rejection), but also when administered therapeutically during an immune response, such as during the active course of an autoimmune disease. The most important aspect of its immunosuppressive mechanism is the inhibition of lymphokine production secreted by activated T cells. The pharmacological effects of CyA are rapid in onset, dose-dependent and often quickly reversible when treatment is stopped.

Animals↗
PubMed1989

Enigmatic action of ciclosporine A on the naloxone-precipitated morphine withdrawal syndrome in mice.

Various alterations of the immune system have recently been reported to attenuate the severity of morphine withdrawal. The effect of the immunosuppressive agent ciclosporine A on the naloxone-induced morphine withdrawal syndrome in the chronically dependent mouse was investigated. Ciclosporine A significantly suppressed stereotyped behaviour such as jumping and forepaw treading while wet shakes were potentiated. Withdrawal diarrhoea was diminished as a consequence of a promotive action of ciclosporine A on the intestine. A ciclosporine derivative, which is devoid of immunosuppressive activity, had no influence on withdrawal signs. The attenuating effect of ciclosporine A was observed at a dose of 20 mg/kg i.p., which is not regarded as immunosuppressive in the mouse. It was also effective in animals lacking an intact immune system as a result of a genetic T-cell defect (nude mouse) or after selective ablation by whole body irradiation. Nude mice and irradiated normal mice developed dependence on morphine to the same extent as normal animals, as could be derived from the severity of their withdrawal signs. These results suggest that an intact immune system is not a necessary prerequisite for ciclosporine A to attenuate morphine withdrawal and that its action may be attributable to mechanisms other than immunosuppression. It is possibly a result of a direct effect of ciclosporine A on the central nervous system structures involved in the behavioural expression of the opiate withdrawal syndrome.

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PubMed1988

Chronic relapsing experimental allergic encephalomyelitis in the Lewis rat: studies on immune regulation.

To study immunoregulation of chronic relapsing experimental allergic encephalomyelitis (CR-EAE) in Lewis rats, we adoptively transferred concanavalin A-activated lymph node cells (LNC) or splenocytes, from hind footpad-inoculated donors at the onset (day 11), or recovery (day 16), of the first attack. Popliteal LNC, especially from day 16 donors, provided significant and dose-dependent, but incomplete, protection of recipients from encephalitogenic challenge; maximal mean delay in EAE onset was 10 days later than controls, with subsequent paralysis reduced more than 6-fold. In contrast, particularly from day 11 donors, superficial inguinal LNC recipients developed actively induced disease of normal severity up to 4 days earlier than CR-EAE controls. Furthermore day 11 EAE splenocytes, but not day 16 ones, adoptively transferred disease into 50-88% of naive recipients. In separate studies, we demonstrated unresponsiveness to active induction of disease in all rats re-challenged during stable late remission, as well as in a minority of animals pretreated with antigen in incomplete Freund's adjuvant. These results suggest an organ-dependent and time-dependent balance between effector and suppressor populations in the model.

Animals↗
PubMed1988

Syngeneic graft-versus-host disease induced by cyclosporine--a reappraisal.

Cyclosporine-induced graft-versus-host disease has been described in lethally irradiated rats and mice following syngeneic bone marrow reconstitution. To further study this apparently CsA-restricted phenomenon, we followed reported protocols by administering CsA orally at 50 or 100 mg/kg/day to irradiated, syngeneically reconstituted C57B1/6 mice. No clinical evidence of GVHD was observed for more than 8 weeks after CsA discontinuation. Ear biopsies and circulating immunoglobulin levels 2-4 weeks after stopping CsA failed to demonstrate histological or serological evidence of GVHD, respectively, compared with mice allogeneically reconstituted with Balb/c marrow. To further follow a previous report, CsA 50 mg/kg/day orally or 10 mg/kg/day intraperitoneally was given to normal C57B1/6 mice prior to using their spleen or bone marrow cells for reconstitution of lethally irradiated syngeneic mice. Clinical monitoring and histological examination of recipients 2-5 weeks after reconstitution again failed to confirm GVHD. Thus our results were uniformly negative in attempting to reproduce syngeneic GVHD in mice. Existing data on rats and humans are reviewed, showing that syngeneic or autologous GVHD is not CsA-restricted and that the syndrome could be equated to the chronic form of GVHD found in rats and patients after allogeneic bone marrow transplantation.

Animals↗
PubMed1988

Mast cell degranulation as a major event in the effector phase of delayed-type hypersensitivity induced by cloned helper T cells.

A kinetic study (0-72 h) was performed on the cellular composition of the exudate in delayed-type hypersensitivity (DTH) induced by the injection of cloned helper T cells into the footpad of C57BL/6J mice. In this model the reaction was maximal at 24 h, as assessed by local swelling. After an initial phase of inflammatory cell infiltration, we observed pronounced degranulation of mast cells, occurring at 15-19 h. Administration of antihistamines shortly before this time significantly inhibited the increase in footpad thickness at 24 h, suggesting mast cell mediators as a major cause of swelling in DTH. Furthermore, a new arrival of inflammatory cells, particularly eosinophils, was clearly correlated with mast cell degranulation. The latter, which might function to suppress local reactions, persisted as the only intact cell type after 48 h. Supplementary examination of peripheral blood smears showed successive peaks of neutrophils (at 3 h), monocytes (at 15 h) and finally eosinophils (after 20 h). These results suggest a local and systemic cascade in DTH which depends on mast cell degranulation for its full expression.

Animals↗
PubMed1988

Preventive and therapeutic effects of cyclosporin and valine2-dihydro-cyclosporin in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat.

Cyclosporin (CS) and valine2-dihydro-cyclosporin [(Val2)DH-CS] were tested in adult Lewis rats with chronic relapsing experimental allergic encephalomyelitis (CR-EAE), induced by the immunization of guinea-pig spinal cord emulsified in complete Freund's adjuvant. The drugs were given orally for 15 or 35 days, at 12.5, 25 or 50 mg/kg/day, starting either on the day of sensitization (preventive treatment) or at one of three subsequent times (therapeutic treatment): the onset of the first attack (protocol A); the onset of the first spontaneous remission (protocol B); and the onset of the second attack (protocol C). Used therapeutically in protocol A, at doses above 12.5 mg/kg/day, both drugs prolonged remission past the end of therapy in more than two-thirds of the treated animals, compared to less than 10% of controls. Trends were similar under protocols B and C. Disease developing after preventive treatment with either drug was predominated by chronic and hyperacute attacks, in contrast to the relapsing course of controls. This pattern was also the result after CS was given therapeutically, whereas (Val2)DH-CS in such circumstances eliminated all further attacks in the majority of rats (58-86% at 25 mg/kg/day) and only minimal disease occurred in the remainder. We conclude that both drugs, in this model, are beneficial during administration; however, in contrast to CS, (Val2)DH-CS possesses an important, curative action when applied therapeutically.

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