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

@article{Pekarski1998TheIE,
  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},
  journal={Autoimmunity},
  year={1998},
  volume={28 4},
  pages={
          235-41
        }
}
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
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References

SHOWING 1-10 OF 18 REFERENCES
Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide
TLDR
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).
TLDR
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
TLDR
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.
TLDR
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
TLDR
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
TLDR
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.
TLDR
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.
TLDR
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
TLDR
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
TLDR
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
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