The Potential Negative Effects of Interleukin-1β in Multiple Sclerosis Patients with MEFV Mutation

Abstract

ÖzetMEditerranean FeVer (MEFV) gen mutasyonlu multipl skleroz hastaları, bu mutasyonu taşımayanlara kıyasla daha hızlı ilerleyen hastalığa sahiptirler.Ancak, bunun mekanizması henüz tam olarak aydınlatılamamıştır. Bu yazı, bu hızlı ilerlemeden sorumlu olabilen interlökin-1β (IL-1β)'nın muhtemel rolünü önermektedir. MEFV geni, pyrin proteinini kodlar ve mutasyonları ailesel Akdeniz ateşine neden olur. MEFV mutasyonları, pyrin fonksiyonunun ortaya çıkmasına yol açar ve IL-1β'nın uygun olmayan salınımıyla sonuçlanır. gene mutation, have faster progression than the non-carriers. However, its underlying mechanism is not well understood. This article proposes the potential role of interleukin-1β (IL-1β) that may be responsible for this rapid progression. Mutations in MEFV, the gene encoding for protein pyrin, cause familial Mediterranean fever, lead to gain of pyrin function, resulting in inappropriate IL-1β release. Interleukin-1β is a major mediator of systemic inflammation and fever, and also it contributes to permeability of the bloodbrain barrier in active lesions of multiple sclerosis. Moreover, IL-1β promotes apoptosis of neurons and oligodendrocytes that produce the myelin sheath, which insulates axons. Thus, inflammatory damage, the blood-brain barrier disfunction, effects of fever on the central nervous system (or Uhthoff's phenomenon), and apoptosis of neurons and oligodendrocytes, which play an important role in the pathogenesis and clinical course of multiple sclerosis, can be induced by increased activation and release of IL-1β in the presence of MEFV gene mutations. Therefore, screening for MEFV mutations in patients with multiple sclerosis and treatment planning with IL-1β targeting drugs for the carriers, may be a logical idea that will be a source of inspiration for scientific studies.