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Biomedical subjects

J F Borel

Publications and source records attributed to J F Borel.

At least 55 records · Page 3Linked to original sources
PubMed1987

The mode of action of immunosuppressive drugs.

The immunosuppression first introduced in the 1950s acted indiscriminately, blocking or damaging all the cells that happened to be in mytosis. The toxic side effects were usually so severe that the overall results were not considered satisfactory. The major drawback to the commonly used combination of steroids and cytotoxic drugs is the high risk of overwhelming infections. The next step was the development of lymphocytotoxic drugs or procedures which were restricted to the elimination of the immunocompetent cells. This was achieved by the use of total lymphoid irradiation, thoracic duct cannulation, antilymphocyte globulin, L-asparaginase and steroids. Steroids not only intervene at many points of the immune response, but they also possess a remarkable anti-inflammatory potency. The current or third stage is that of immunopharmacology, which is characterized by selective immunoregulation using compounds or methods that specifically modulate defined subpopulations of immunocompetent cells. Ciclosporin is the first drug that fulfilled these requirements to some extent and that has proved of permanent clinical value. The new technology of monoclonals has allowed the production of highly specific antibodies directed toward lymphocyte subsets. The modulation of lymphokines is another potential approach for both immunosuppression and immunostimulation. The final phase of immunosuppression will be the induction of antigen-specific depression of allograft reactivity. Classical transplantation tolerance has been induced in a developing immune system, but it is virtually impossible to achieve in a fully developed immune system.

Antibody Formation↗
PubMed1987

[[Cyclosporin forever?].

The author presents a summarized review concerning the use of cyclosporine in the control of graft rejection. He insists on the need to reduce as far as possible the cyclosporine dosage applied. This can be achieved in association with other drugs, such as azathioprine and/or steroids. The mechanism of action due to cyclosporine seems to be linked both with some modifications in the graft's antigenicity, mainly the disappearance of MHC class II bearing cells, but above all with profound modifications in lymphokine secretion resulting in the inhibition of DTH responses and with the selective activation of suppressor cells. The author insists finally on the importance of cyclosporine not only for the medical treatment of rejection, but also for its significance as a research tool in immunology.

Cyclosporins↗
PubMed1985

Comparison of the pharmacological profiles of cyclosporine, (Nva2)-cyclosporine and (Val2)dihydro-cyclosporine.

The pharmacological profiles of two new derivatives of the immunosuppressive drug, cyclosporine, is presented here. (Nva2)-CS has very similar properties to CS, but lacks the nephrotoxic side-effects. This derivative appears to be a potential successor to cyclosporine. (Val2)DH-CS seems to have a different spectrum of activities. It does not suppress humoral immunity and allograft rejection, but suppresses some types of cell-mediated immune responses. This derivative may prove useful in autoimmune situations where T cells are involved in the disease process.

Animals↗
PubMed1982

Immunosuppression by cyclosporin A of experimental allergic encephalomyelitis.

Cyclosporin A (CsA), an immunosuppressant which acts selectively on antigen-responding T cells, was tried in the treatment of experimental allergic encephalomyelitis (EAE). The drug was highly effective in preventing the appearance of clinical and pathological signs of EAE in rats, guinea pigs and monkeys. Treatment of the established disease also reduced the incidence and severity of symptoms, and significantly reduced the number of inflammatory lesions in the central nervous system.

Animals↗
PubMed1982

Immunosuppressive effect of cyclosporin A in two lymphocyte transfer models in rats: comparison of in vivo and in vitro treatment.

The immunosuppressive effect of CS-A was first studied in the assay for local GvHR. 3 X 10(6) viable spleen cells from LEW rats were injected into one foot pad of LEW X BN hybrids and both PLN were weighed 7 days later. Treatment of the recipients with 3 doses of 50 mg/kg/day of CS-A suppressed this local GvHR. The effect was more pronounced when treatment started at the time of cell transfer rather than a few days before peak response. In vitro incubation of the cellular inoculum with CS-A also prevented local GvHR. Histology of the PLN confirmed the quantitative results expressed by the PLN index. CS-A was further investigated in the EAE model in LEW rats. It protected rats sensitised with spinal cord emulsified in complete Freund's adjuvant for as long as they were treated with CS-A. Treatment delayed until after the appearance of EAE also markedly improved their condition. Oral treatment of recipients with 50 mg/kg/day CS-A prevented the development of adoptive EAE following the transfer of lymphoid cells conditioned in vitro. The presence of 0.1-1.0 microgram CS-A in the medium of the sensitised lymphoid cells also inhibited the adoptive transfer of EAE. Finally, if the cells for the adoptive transfer were derived from CS-A-treated sensitised donors, they failed to induce EAE. Histological examination supported the symptomatic findings.

Animals↗
PubMed1981

Cyclosporin A: effects on the mouse thymus.

Cyclosporin A (CY-A), an immunosuppressive cyclic endecapeptide, causes thymus weight reduction in mice 4 days after single oral administration. This effect was compared with that of hydrocortisone acetate (HCA), or of azathioprine (AZ). The latter had no effect on thymus weight, whereas HCA induced a marked reduction 2 days after administration. A possible mediation by the pituitary adrenal gland system (PAG) of the CY-A induced effect was suggested by the observation of an elevated corticosterone plasma level after CY-A administration and by the prevention of the thymocytolytic effect by adrenalectomy. However, the immunosuppressive activity of CY-A in humoral immunity and cell mediated tests was not affected by adrenalectomy. It must therefore be concluded that the immunosuppression produced by CY-A in vivo is not mediated by stimulation of the PAG system, contrary to its effect on the mouse thymus, which is a glucocorticosteroid effect.

Adrenalectomy↗
PubMed1980

Studies on the mechanism of action of cyclosporin A.

The mechanism of cyclosporin A (CS-A), a compound known to act selectively on the immunocompetent lymphocyte, was investigated in a series of in vitro studies. CS-A, provided it was added simultaneously with mitogen, inhibited the incorporation of tritiated uridine and thymidine into mouse spleen cells and human peripheral blood lymphocytes. Addition of CS-A 48 h after onset of culture did not affect cell division, indicating that it acted at an early stage of lymphocyte stimulation, exerted no inhibitory effect on lymphoblasts and did not possess anti-mitotic activity. It was further shown that CS-A was not lymphotoxic and that its effect was reversible, because suppressed spleen cells recovered their proliferative capacity after a 24 h elution period. Inhibition of PFC in the Mishell-Dutton assay provides evidence of an anti-T helper cell action of CS-A.

Animals↗