Lipoic acid modulates inflammatory responses of monocytes and monocyte-derived macrophages from healthy and relapsing-remitting multiple sclerosis patients

Sarah E. Fiedler, Rebecca I. Spain, Edward Kim, Sonemany Salinthone

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Multiple sclerosis (MS) is a disabling neuroinflammatory 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 proinflammatory 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 adenosine monophosphate (cAMP) in monocytes and monocyte-derived macrophages (MDMs). LA treatment resulted in a generally less inflammatory phenotype of monocytes and MDMs from healthy controls, and (to a lesser degree) MS donors. LA inhibited monocyte secretion of cytokines relevant to MS in monocytes, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β; LA effects on secretion of these cytokines in MDMs were mixed with inhibition of TNF-α and IL-6, but stimulation of IL-1β, the latter perhaps as a result of altered macrophage polarization. LA inhibited phagocytosis in both monocytes and MDMs, and increased cAMP levels in monocytes. LA may modulate inflammatory cytokine secretion and phagocytosis via a cAMP-mediated mechanism.

Original languageEnglish (US)
Pages (from-to)107-115
Number of pages9
JournalImmunology and Cell Biology
Volume99
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • cyclic AMP
  • lipoic acid
  • macrophage
  • monocyte
  • multiple sclerosis
  • phagocytosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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