The interplay between endoplasmic reticulum stress and inflammation in multiple sclerosis.

Endoplasmic reticulum (ER) stress is one of the hallmarks of neurodegenerative diseases. This study aimed to investigate the role of ER stress in interaction with inflammatory markers in patients with multiple sclerosis (MS). The participants in the current study were recruited in two age and sex-matched groups: 44 recently diagnosed MS patients and 53 control subjects. Differential gene expression of C/EBP homologous protein (CHOP), 78-kDa glucose-regulated protein (GRP78), and circulating levels of interleukin (IL)-1β and tumor necrosis factor (TNF-α) were assessed in MS patients and controls. The results showed that serum levels of TNF-α were significantly higher in MS patients than in the control group (p = 0.01), but not IL-1β serum levels. As for ER stress markers, there were no changes in CHOP expression levels in MS patients compared to the control group (p = 0.2). In contrast, GRP78 showed significant upregulation in MS patients compared to the control group (p = 0.0001). This study showed that the interaction between GRP78 and TNF-α influences the risk of MS (beta = 1.43, 95%CI:1.09-1.87, p = 0.01). Our data suggest that the interaction between TNF-α and GRP78 may modulate ER stress in MS patients.