Experession, production and possible role of interleukin 10 and tumor necrosis factor during experimental autoimmune encephalomyelitis in AO and DA rats

Multipla skleroza (MS) je hronična inflamatorna i neurodegenerativna bolest centralnognervnog sistema (CNS) sa autoimunskom patogenezom. Najčešće pogađa populacijuizmeđu 20-40 godina, češća je kod žena nego kod muškaraca, kao i u Evropi i SevernojAmerici u odnosu na druge delove sveta. Iako još uvek nije jasno definisan uzroknastanka ove bolesti, smatra se da su u njenoj osnovi kompleksne interakcije izmeđurazličitih gena i faktora sredine.Eksperimentalni autoimunski encefalomijelitis (EAE) je najkorišćeniji animalni modelMS-a. Indukuje se najčešće u glodarima i to imunizacijom, korišćenjem homogenatatkiva CNS-a, mijelina ili nekih od proteina mijelina koji se mešaju sa adjuvansom.Nakon imunizacije, CD4+ T-ćelije specifične za antigen CNS-a proliferišu idiferenciraju se u drenirajućem limfnom čvoru, nakon čega dolazi do njihove migracijei širenja po celom organizmu. Deo ćelija specifičnih za antigene nervnog sistema odlaziu CNS, prolazi kroz krvno-moždanu barijeru i u perivaskularnom prostoru prepoznajeantigen za koji je specifičan. Nakon susreta sa antigenom T-ćelije bivaju reaktivirane,počinju da produkuju odgovarajuće citokine, aktiviraju lokalne ćelije i dalje privlačeinflamatorne ćelije u CNS. Na ovaj način nastaje inflamatorna reakcija koja zaposledicu ima uništavanje mijelinskog omotača, a u određenim slučajevima i aksonadovodeći tako do neurodegeneracije.Citokini predstavljaju bitne medijatore svakog inflamatornog procesa. IL-10 je antiinflamatornicitokin sa osnovnom ulogom u zaštiti tkiva i ograničavanju preteranoginflamatornog odgovora. Sa druge strane, TNF je predstavniik pro-inflamatorne grupecitokina koji ima ključnu ulogu medijatora akutne i hronične sistemske inflamatornereakcije. Oba citokina su dosta proučavana u EAE modelu, gde se IL-10 u najširemsmislu smatra protektivnim, dok se TNF uglavnom smatra štetnim i odgovornim zapojačavanje inflamatorne rekcije...Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of thecentral nervous system (CNS) with a proposed autoimmune pathogenesis. It mainlyaffects population between 20-40 years of age, more often women in comparison to menAlso, it is more often in Europe and north America comparing to other parts of theworld.. The cause of this disease is still not well defined, but it is thought to be complexinteraction between genes and different environmental factors.Experimental autoimmune encephalomyelitis (EAE) is the most commonly used MSanimal model. It is mostly induced in rodents by using spinal cord homogenate, myelinor some of the myelin’s proteins and mixing them with adjuvants. After theimmunization antigen specific CD4+ T cells proliferate and differentiate in draininglymph nodes after which they migrate and spread all around the body. One part of theantigen specific cells goes to CNS, crosses blood-brain barrier and enters theperivascular space where it recognizes antigens which they are specific for. Afterencountering the antigens T cells are reactivated and they start producing cytokines,activate local cells and attract other inflammatory cells in to the CNS. This is howinflammatory reaction begins leading to distraction of myelin sheet or even axons insome cases, finally causing neurodegeneration.Cytokines are important mediators of every inflammatory process. IL-10 is an antiinflammatorycytokine with a primary role in tissue protection and restriction ofinflammatory response. On the other hand, TNF is a classical pro-inflammatorycytokine which mediates acute and chronic systemic inflammatory reaction. The role ofboth these cytokines has been well studied in EAE model, where IL-10 is considered tobe protective while TNF is mostly thought of as deleterious and responsible forincreasing the inflammatory reaction..