Compared to patients with Intracranial hypertension, the following CSF proteins: Extracellular Superoxide dismutase (ECSOD) at Cys195, α1-antitrypsin (A1AT) at Cys232, Phospholipid transfer protein (PLTP) at Cys318, Alpha-2-HS-glycoprotein at Cys340, Ectonucleotide pyrophosphate (ENPP-2) at Cys773, Gelsolin at Cys304, Interleukin-18 (IL-18) at Cys38 and Ig heavy chain V III region POM at Cys22 were found to be glutathionylated in patients with multiple sclerosis during a relapse.
Variants associated with low serum levels of IL-18 were significantly less frequent in MS patients than in controls, suggesting a protective role of diminished IL-18-mediate inflammation in MS development.
Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is involved in the maturation and secretion of IL-1β and IL-18 and, thus, plays a key role in the pathogenesis of many inflammatory conditions, including multiple sclerosis (MS).
Finally, transcriptional over-expression of MR1 - which presents cognate antigens to MAIT cells - and of the activating cytokines IL-18 and IL-23 was evidenced in MS lesions, suggesting that the CNS microenvironment is suited to activate the few infiltrating MAIT cells.
Aim of the present study was to determine if any relation exists between IL-18-137C/G and -607C/A gene promoter polymorphisms on the individual susceptibility of multiple sclerosis and also to investigate the possible effect of IL-18 activity regarding this kind of polymorphism and MS.
We show in this study that IL-18-binding protein (IL-18bp), the endogenous inhibitor of the Th1-promoting cytokine IL-18, is upregulated by IFN-gamma in resident microglial cells in the CNS during multiple sclerosis-like disease in mice.
An increased IL-18 expression, potentially augmented at the mature protein level, may indicate a pathway worth considering in future therapeutic strategies in MS.
These results demonstrated that IL-18 has an important role in augmenting Th-1 type immune responses in MS and may be involved in immune changes that occur when patients enter the progressive stage.