Recent studies of gut-blood barrier have showed that short peptides of food proteins are transported to the blood easier  than aminoacids. Special  system presenting antigens in gut is formed. This process  presenting food  peptides and suppressing  of immunological respons to them is called oral tolerance. Recently, it has been  proposed  to apply it to  treatment  of autoimmune  diseases as multiple sclerosis, rheumatoid arthritis, uveitis, diabetes type 2.

The aim of our study was  to  use  hydrolizate of spinal cord proteins which is the mixture of neuropeptides  obtained after hydrolysis of an undenatured homogenate of proteins digested with pepsin  as an antigen for feeding the experimental animals/rats/. After induction of tolerance   animals were immunised by injection of guine pig spinal cord  homogenate with Freund’s adjuvant  to evoke  experimental allergic encephalomyelitis/EAE/, which is  an animal model  of sclerosis multiplex.  Clinical  course have been observed, histopathological study, ultramicroscopic study  and   metaloproteases determination in blood  were done. Study of limphocyte proliferation and level of cytokine Il-4 and Il-10, Inf-γ, and TGF-β were also performed.

Clinical course of EAE post hydrolyzate treatment has been milder than control. MBP and TNF  in brains  were decreased. Metaloproteases increased in EAE, after hydrolizate treatment  were dimished by 30%.  Some  changes in blood-brain barrier/BBB/ as opened tight junction and other changes  in early phase of EAE as  karioskeletal damage with vesicular structures in karioplasm, compartmentalisation  of the  endoplasmic reticulum  in perikarium, large cisterns of the Golgi apparatus, increased activity of microglial cells with numbers  of phagolisosomes, desorganisation  of sheets of myelin, neoangiogenesis  of parenchyma of the cerebral cortex   has been dimished. Mechanism of this effect  is probably  through  active suppression  involving  diminishing  lymphocytes  production of  interferon gamma  and   interleukine-10 as well as   increasing  production of TGF-α and  interleukin-4. Above  results  indicate on  possible clinical implication of oral  tolerance  in  treatment  of multiple sclerosis. Results strongly indicate  that mixture of neuropeptides in spinal cord hydrolisate  given orally diminished  immunological response to myelin antigens.

Acknowledgement: This work has been partially supported by Polish Grant G-6412007/01

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