Lipoic acid modulates inflammatory response in RRMS

[NHE]

Lipoic acid modulates inflammatory responses of monocytes and monocyte-derived macrophages from healthy and relapsing-remitting multiple sclerosis subjects
Immunol Cell Biol. 2020 Aug 6. doi: 10.1111/imcb.12392.

Multiple Sclerosis (MS) is a disabling neuro-inflammatory disease. Its etiology is unknown, but both oxidative stress and inflammation appear to be involved in disease pathology. Macrophages are the predominant cell type in acute inflammatory brain lesions in MS. Macrophages produce pro-inflammatory and toxic molecules that promote demyelination and are key players in phagocytosis/degradation of myelin sheathes. Lipoic acid (LA) is an inexpensive, endogenously-produced small molecule that exhibits antioxidant and anti-inflammatory effects. Treatment with LA is protective in MS and other inflammatory diseases. To examine the mechanism(s) by which LA may attenuate inflammatory lesion activity in MS, we used healthy control and MS cells to evaluate the effects of LA on levels of inflammatory cytokines, phagocytosis, and the immunomodulator cyclic AMP (cAMP) in monocytes and monocyte-derived macrophages (MDM). LA treatment resulted in a generally less inflammatory phenotype of monocytes and MDM from HC, and (to a lesser degree) MS donors. LA inhibited monocyte secretion of cytokines relevant to MS in monocytes, including TNF-α, IL-6 and IL-1β; LA effects on secretion of these cytokines in MDM was mixed with inhibition of TNF-α and IL-6, but stimulation of IL-1β, the latter perhaps due to altered macrophage polarization. LA inhibited phagocytosis in both monocytes and MDM, and increased cAMP levels in monocytes. LA may modulate inflammatory cytokine secretion and phagocytosis via a cAMP-mediated mechanism.