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Biomedical subjects

J F Borel

Publications and source records attributed to J F Borel.

At least 19 recordsLinked to original sources
PubMed1995

Immunoregulation and drug treatment in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat.

Chronic relapsing experimental allergic encephalomyelitis (CR.EAE) was induced by immunizing Lewis rats with total guinea-pig spinal cord (GPSC) tissue emulsified in enriched complete Freund's adjuvant (CFA). The proliferative responses of draining inguinal and popliteal lymph node cells to GP.MBP, purified protein derivative (PPD) and concanavalin A (ConA) appeared significantly modulated according to the clinical state of the animals. Responses appeared significantly decreased in both lymphoid compartments during the recovery periods compared with that during relapses. Therapeutic treatment of CR.EAE with cyclosporin and different lysolecithin derivatives, such as ET-18-OCH3, SRI 62-843 and MLS 266-337, starting at the spontaneous remission of the first disease bout, could suppress the manifestation of further relapses. Whereas cyclosporin only delayed the onset of the disease relapse until discontinuation of treatment, all lysolecithins showed a curative effect in most animals. Plasma corticosterone levels measured at different time points in placebo, cyclosporin and MLS 266-377-treated rats showed a strong correlation with the clinical state of the animals. High corticosterone levels were detected during stages of acute paralysis, whereas a decrease to normal levels was noted during each recovery phase.

Animals↗
PubMed1994

The viable motheaten (mev) mouse--a new model for arthritis.

Homozygous mev mice are first identified at the age of 3-4 days by focal depigmentation of the skin, followed by patchy absence of hair and by necrotic lesions on paws, tail and ears. Of particular interest are the inflammatory reactions in the paws of these animals which consist mainly of polymorphonuclear and mononuclear cell infiltration in the subcutaneous tissue extending to the periosteum and joint, resulting in focal destructive arthritis and osteomylitis. These lesions are to some extent reminiscent of an acute form of rheumatoid-like arthritis. Since mev mice are sterile, a limited number of symptomatic offspring can be obtained by cross-breeding their heterozygous siblings which are phenotypically not distinguishable from mice lacking this mutation. In order to produce a sufficient number of diseased animals for performing pharmacological studies, we have established a model by transferring this disease in lethally irradiated, 8- to 10-week-old syngeneic mice which were grafted with mev spleen cells. Such reconstituted recipients develop first inflammatory symptoms of the paws 2 to 3 weeks after cell transfer. The arthritic inflammation finally affects all paws and toes by 30 to 50 days. This procedure increased the number of mev-like mice expressing arthritis, allowing assessment of the effects of standard reference drugs used in the therapy of rheumatoid arthritis (RA). The immunosuppressants cyclosporin and rapamycin and the steroid dexamethasone at therapeutic concentrations exert a strong inhibitory effect on the development of arthritis in this novel model. In contrast, the non-steroidal anti-inflammatory drug phenylbutazone shows only a moderate effect. These results indicate the particular sensitivity of this model for efficacy of potentially new therapeutic but non-cytostatic compounds for clinical use.

Animals↗
PubMed1994

Molecular mechanisms of immunosuppressive agents.

Recent data on the molecular mechanism of some immunosuppressive drugs provide strong support for the fascinating postulate that CSA and FK506 work by binding to immunophilins and then, as a drug-immunophilin complex, inhibiting the calcium-activated protein phosphatase, calcineurin. This inhibition could result in an altered modification pattern of the cytoplasmic components of transcription factors, thereby disturbing their nuclear translocation, which is a prerequisite for proper IL-2 transcription. It looks as if, with the immunosuppressive microbial metabolites as molecular probes, the pieces of this complex signal transduction puzzle are starting to fit together! Once the details of the chain of events along the T-cell signaling pathways are known, the molecular structures involved will provide new tools to be used in the search for and the rational design of new and improved therapeutic agents.

Amino Acid Isomerases↗
PubMed1992

SRI 62-834, a cyclic ether analogue of the phospholipid ET-18-OCH3, displays long-lasting beneficial effect in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. Comparison with cyclosporin and (Val2)-dihydrocyclosporin effects in clinical, functional and histological studies.

The therapeutic effect of the ether phospholipid SRI 62-834, which lacks the characteristics of an immunosuppressive agent, was compared with those of two immunosuppressive drugs, cyclosporin and valine2-dihydrocyclosporin, in a rat model of chronic relapsing experimental allergic encephalomyelitis (CR-EAE). Drug treatment was initiated at the beginning of the first spontaneous remission on day 15 and was discontinued on day 31. Whereas the untreated rats experienced two paralytic relapses around days 21 and 31, the progression of CR-EAE was prevented during the period of drug administration. Protection with both cyclosporin and its derivative was complete, but SRI 62-834 only attenuated the clinical disease. The absence of paralytic symptoms was reflected by a distinct reduction in mononuclear cell infiltration in the central nervous system at days 21 and 31 in treated animals. The main difference between the two drug classes became apparent after withdrawal of therapy. Discontinuation of SRI 62-834 resulted in a long-lasting beneficial effect, with the rats remaining clinically normal and showing no histopathological changes. However, cyclosporin only delayed the clinical symptoms which reappeared after cessation of treatment. The exacerbated paralytic relapse, which followed about 1 week later and was associated with severe perivascular cell infiltrates and tissue destruction, subsequently became chronic in several animals. By contrast, withdrawal of valine2-dihydrocyclosporin partially prevented disease relapse and markedly reduced severity of symptoms without progression of a chronic disease. These results demonstrate the clear differences in the mode of action of these compounds in CR-EAE and suggest that SRI 62-834 could be an interesting candidate for the treatment of multiple sclerosis.

Animals↗
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.

Animals↗
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↗