Adipokines as Immune Cell Modulators in Multiple Sclerosis

Abstract

Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine function. To explore the role of adipokines in MS pathology, we will here review the reciprocal effects of adipokines and immune cells and summarize alterations in adipokine levels in MS patient cohorts. Finally, we will discuss proof-of-concept studies demonstrating the therapeutic potential of adipokines to target both neuroinflammation and neurodegeneration processes in MS.

Keywords: adipokines; demyelination; immunology; multiple sclerosis; neurodegeneration; neuroinflammation; obesity.

Figure 1

Proposed hypothesis: Obesity and MS can lead to altered adipokine release from white adipose tissue (WAT) into circulation. This results in the activation of inflammatory pathways and increased infiltration of immune cells in the CNS. On the other hand, increased levels of pro-inflammatory cytokines in MS such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interferon γ (IFN-γ) further stimulate the release of pro-inflammatory adipokines from the WAT and disrupt adipokine signaling, creating a detrimental positive feedback loop. MS, multiple sclerosis; BBB, blood–brain barrier.