The inhibitory effect in experimental autoimmune encephalomyelitis by the immunomodulatory drug Linomide (PNU-212616) is not mediated via release of endogenous glucocorticoids.

  title={The inhibitory effect in experimental autoimmune encephalomyelitis by the immunomodulatory drug Linomide (PNU-212616) is not mediated via release of endogenous glucocorticoids.},
  author={O. Pekarski and J. Bj{\"o}rk and G. Hedlund and G. Andersson},
  volume={28 4},
The immunomodulatory drug Linomide (PNU-212616) is an efficient inhibitor of experimental autoimmune encephalomyelitis (EAE) and a variety of other models of autoimmunity. The mechanism of action of the drug is, however, incompletely resolved. It was recently suggested that Linomide might exert its immunomodulatory activity by stimulation of the hypothalamic-pituitary-adrenal axis. To investigate the relevance of this mechanism of action, we monitored the plasma levels of endogenous… Expand
Suppression of experimental autoimmune neuritis by ABR-215062 is associated with altered Th1/Th2 balance and inhibited migration of inflammatory cells into the peripheral nerve tissue
The therapeutic effects of ABR-215062 evaluated in experimental autoimmune neuritis (EAN), a CD4(+) T cell-mediated animal model of Guillain-Barré syndrome in man, indicate that ABR the immunoregulator may mediate its effects by regulation of Th1/Th2 cytokine balance and suggest that ABRs is potentially a new chemical entity for effective treatment of autoimmune diseases. Expand
Beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats.
The results, when viewed globally, indicate that beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, which has a more severe course in adrenalectomized rats and beta- adreno receptor-mediated mechanisms operate in Adrenalectomy-induced aggravation of the disease. Expand
Glucocorticoids in multiple sclerosis and experimental autoimmune encephalomyelitis
This review will critically discuss what is learned so far from the analysis of animal models of the molecular mode of therapeutic and endogenous glucocorticoid action in multiple sclerosis to be able to further improve the management of multiple sclerosis using this class of drugs. Expand
Clinical and experimental data on the use of laquinimod for the treatment of multiple sclerosis
In the recently published Phase III ALLEGRO trial, laquinimod 0.6 mg/day showed a reduction of relapse rates and even more pronounced effects on disability progression compared with placebo, and the potential to add... Expand
The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis
A new orally active drug, laquinimod (ABR-215062), was shown to completely inhibit the development of murine acute experimental autoimmune encephalomyelitis (EAE). Furthermore, leukocyte infiltrationExpand
End-point effector stress mediators in neuroimmune interactions: their role in immune system homeostasis and autoimmune pathology
This work has discovered the influence of CAs and GCs on fine-tuning thymocyte negative selection and pointed to the putative CA-mediated mechanisms underlying this influence, and shown that CAs are implicated in the regulation of regulatory T-cell development in the thymus. Expand
Differential effects of low frequency, low intensity (<6 mG) nocturnal magnetic fields upon infiltration of mononuclear cells and numbers of mast cells in Lewis rat brains.
It is suggested that weak magnetic fields can affect the infiltration of immunologically responsive cells and the presence of mast cells in brain parenchyma. Expand
Synthesis and biological evaluation of new 1,2-dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for treatment of autoimmune disorders: structure-activity relationship.
Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II). Expand
Synthesis and Antimicrobial Activity of Novel 4-Hydroxy-2-quinolone Analogs
The data suggest that the 4-hydroxy-2-quinolone is a promising framework for the further development of new antimicrobial agents, especially for antifungal treatment. Expand
Solid-phase synthesis of quinolinone library.
The ability some of these compound to inhibit the release of IL-1β, a cytokine involved in the immune response was measured, and they showed about 50% inhibition at 10 μM. Expand


Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide
Results indicate that modulation of the immune system with linomide leads to complete inhibition of experimental autoimmune encephalomyelitis in the absence of systemic immunosuppression, and Linomide could therefore be of use in future clinical trials for the treatment of human autoimmune demyelinating disorders. Expand
Treatment of chronic-relapsing experimental autoimmune encephalomyelitis with the synthetic immunomodulator linomide (quinoline-3-carboxamide).
Linomide regulates autoimmunity in the absence of systemic immunosuppression, and since linomide is very well tolerated in experimental animals and humans, it might be used in the treatment of multiple sclerosis. Expand
Immunomodulation of experimental autoimmune myasthenia gravis with linomide
Linomide may constitute a new immunomodulating agent for the treatment of myasthenia gravis and inhibition of clinical signs of EAMG was observed in the EAMg rat model. Expand
Linomide increases plasma corticosterone in normal rats, but does not prevent the inhibitory action of IL-1 on beta-cells in vivo or ex vivo.
Linomide does not seem to exert its protective effect on IDDM development via inhibition of interleukin 1 action on islet insulin release or NO production, but the increase in plasma corticosterone may contribute to the understanding of the immunomodulatory effects of Linomide. Expand
A reduction in serum glucocorticoids provokes experimental allergic encephalomyelitis
GCCs modified the course of experimental allergic encephalomyelitis in Lewis rats, a model of inflammatory CNS disease, and continuous treatment with dexamethasone completely blocked EAE and counteracted the effects of endogenous GCCs and worsened EAE. Expand
Linomide, a novel immunomodulator that prevents death in four models of septic shock
Pharmacological doses of the immunomodulator linomide prevent death in all four models of lethal septic shock and inhibit the secretion of tumor necrosis factor, one of the major intermediate effector molecules of SEB and LPS toxicity. Expand
Effects of LS-2616 administration upon the autoimmune disease of (NZB x NZW) F1 hybrid mice.
It is suggested that LS-2616 may be useful in the treatment of autoimmune disease in man as well as control groups treated with cyclophosphamide and physiological saline. Expand
The role of the neuroendocrine system in determining genetic susceptibility to experimental allergic encephalomyelitis in the rat.
It is shown that PVG rats that had been adrenalectomized developed severe disease from which they do not recover, and resistance to the induction of EAE could not be abrogated by adrenalectomy in all strains of rats studied. Expand
Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids
It is concluded that endogenous corticosterone release in rats with EAE plays an essential role in the spontaneous recovery that is observed in this condition, and the subsequent refractory phase that is characteristic of rats that have recovered from EAE induced by active immunization with MBP is not associated with chronically elevated cortic testosterone levels. Expand
Experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating disease.
  • R. Swanborg
  • Medicine
  • Clinical immunology and immunopathology
  • 1995
It is clear that important lessons can be learned from the detailed investigation of animal models that may be applicable to human immunological disorders. Expand