Relation between Pro-inflammatory Cytokines and Acetylcholine Levels in Relapsing-Remitting Multiple Sclerosis Patients

Abstract

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder. Since acetylcholine (ACh) is known to participate in the inflammatory response, we investigated the possible relationship between pro-inflammatory cytokines and acetylcholine levels in relapsing-remitting multiple sclerosis (RR-MS) patients. Levels of ACh and pro-inflammatory cytokines IL1-β and IL-17 were measured both in cerebrospinal fluid (CSF) and sera of 22 RR-MS patients in the relapsing phase and in 17 control subjects affected by other non-neurological diseases (OND). We observed higher levels of pro-inflammatory cytokines such as IL-1β and IL-17 in both CSF and serum of RR-MS patients compared to control subjects. Moreover, ACh levels were lower in CSF and serum of RR-MS patients compared to levels of control subjects. Although the relationship between high inflammatory cytokine levels and low ACh levels need to be further investigated in the future, our data suggest that IL-1β, and cytokines induced by it, such as IL-17 and ACh, may be involved in the pathogenesis of MS.

Decreased Level of sRAGE in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset

“…We found that PBMC expression of IL-6 positively correlated with HMGB1 and S100A12, and that PBMC expression of IL-1α was higher, although not significantly (p = 0.086, q = 0.057), in MS patients compared with controls. Both IL-6 and IL-1α have been implicated in the pathogenesis of neuroinflammation in MS [5,31,32,33], and, in accordance with our results, associated with early MS. On the other hand, we found that the expression of IL-10, a potent anti-inflammatory cytokine, was lower in PBMCs of MS patients, concordant with several studies of neuroinflammatory disorders [5,15,33]. IL-10 could be induced by type I IFN in monocytes, macrophages and CD4+ T lymphocytes [19], and represents an important negative feedback mechanism to downregulate uncontrolled production of proinflammatory cytokines (IL-1β, IL-6, IL-17, TNF-α), protecting brain homeostasis [5,16,33].…”

“…Using cultured synovial fibroblasts and macrophages, it was shown that HMGB1 exhibits enhanced proinflammatory activity by binding to cytokines, specifically IL-1β and TNF-α [29,30]. Therefore, we proposed that inflammation may be potentiated by a complex formation of HMGB1 with IL-1β and TNF-α, found to be elevated in the CSF of RR-MS patients [5,16], but our study could not detect an increase in any of these molecules. The lack of difference compared with control samples indicates that the described pathogenic mechanism is not important for MS at the disease onset.…”

“…The pathogenesis of MS involves disturbed cytokine production, including upregulation of proinflammatory cytokines [IL-6, IL-17, IL-1, tumor necrosis factor (TNF)-α, IL-22 and CCL20], and downregulation of anti-inflammatory cytokines (IL-3, IL-4 and IL-10) [2,3,4,5,6]. Proinflammatory cytokines accumulate in MS lesions, suggesting that their increased production may impair cellular defense mechanisms, facilitating demyelination [2,7,8].…”

Hypoxia-like tissue injury and glial response contribute to Balo concentric lesion development

“…The genes for both IL-1β and CCL2 carry multiple HIF-1 binding sites in their promoter regions and exhibit expression that is upregulated by hypoxia in astrocytes via HIF-1α expression. 6,7 IL-1β is a proinflammatory cytokine that may be associated with the progression of multiple sclerosis, 8 and chronic IL-1β expression can induce reversible demyelination. 9 In addition, elevated CCL2 expression has been detected in acute and chronic multiple sclerosis plaques, particularly in hypertrophic astrocytes.…”

Acute and long-term exposure to chlorpyrifos induces cell death of basal forebrain cholinergic neurons through AChE variants alteration

“…A commercial colorimetric/fluorimetric kit (Abcam, Cambridge, UK) (Reale et al, 2012) was used to detect the ACh release in culture medium. Briefly, the culture medium was collected after 24 h and 14 days CPF treatment and spun at 800 Â g. Subsequently, the supernatant was lyophilized, and reconstituted in 50 ml Choline Assay Buffer, and stored at À80 C until further analysis.…”