Adipokines as immune cell modulators in multiple sclerosis

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 dete-rioration 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 devel-oping 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 modifi-cation 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 adi-pokine 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

Adipokines as Immune Cell Modulators in Multiple Sclerosis

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

Correction to:Disc inflammation and Modic changes show an interaction effect on recovery after surgery for lumbar disc herniation (European Spine Journal, (2019), 28, 11, (2579-2587), 10.1007/s00586-019-06108-9)

In Tables 3 and 4: In the first column and row, the text reads “Mixed model test (patients with Modic changes)”. This should have been just “Mixed model”. The complete correct Tables 3 and 4 are given below

Disc inflammation and Modic changes show an interaction effect on recovery after surgery for lumbar disc herniation

Purpose: To study the interaction between Modic changes (MC) and inflammation by macrophages in the disc, in relation to clinical symptoms before and after discectomy for lumbar disc herniation. Methods: Disc tissue was embedded in paraffin and stained with haematoxylin and CD68. Subsequently, tissue samples were categorized for degree of inflammation. Type of MC was scored on MRI at baseline. Roland Disability Questionnaire (RDQ) score and visual analogue scale for back pain and leg pain separately were considered at baseline and 1-year follow-up post-surgery. Main and interaction effects of MC and inflammation were tested against clinical outcome questionnaires. In addition, this analysis was repeated in bulging and extruded discs separately. Results: Disc material and MRI’s of 119 patients were retrieved and analysed. Forty-eight patients demonstrated mild inflammation, 45 showed moderate inflammation, and 26 showed considerable inflammation. In total, 49 out of 119 patients demonstrated MC. Grade of disc inflammation did not associate with the presence of MC. At baseline, no main or interaction effects of MC and inflammation were found on the clinical scores. However, during follow-up after discectomy, significant interaction effects were found for RDQ score: Only in patients with MC at baseline, patients remained significantly more disabled (3.2 points p = 0.006) if they showed considerable disc inflammation compared to patients with mild inflammation. The additional analysis showed similar results in extruded discs, but no significant effects in bulging discs. Conclusions: An interaction effect of MC and disc inflammation by macrophages is present. Only in patients with MC, those with considerable inflammation recover less satisfactory during follow-up after surgery. Graphic abstract: These slides can be retrieved under Electronic Supplementary Material.[Figure not available: see fulltext.]

Gadolinium Enhancement Is Not Associated With Disc Inflammation in Patients With Sciatica

STUDY DESIGN: Retrospective observational histological study. OBJECTIVE: To evaluate the reliability of gadolinium enhancement as a marker for inflammation by associating gadolinium enhancement findings with the degree of inflammation as measured by macrophage infiltration in disc material retrieved during disc surgery in patients with sciatica. SUMMARY OF BACKGROUND DATA: Disc inflammation often occurs in sciatica patients, a noninvasive tool that is used to assess disc inflammation is Gadolinium enhanced MR imaging. METHODS: Disc tissue was retrieved from patients in the Sciatica trial (N = 119), a multicenter randomized controlled trial in patients with sciatica. Disc tissue was embedded in paraffin and stained with hematoxylin and CD68. Tissue samples were categorized as mild (0-10 macrophages/cm), moderate (10-100 macrophages/cm), and considerable (>100 macrophages/cm) inflammation. Of the 119 MRIs, 96 were additionally performed with contrast-enhanced gadolinium. RESULTS: Seventy-four patients showed gadolinium enhancement of the disc herniation and 26 of the nerve root. Degree of inflammation by macrophages was not associated with gadolinium enhancement of nerve roots or herniated discs. These results did not change if the patient groups with and without Modic type 2 changes were evaluated separately. Furthermore, no associations were observed between gadolinium enhancement and presence of Modic type 2 changes. CONCLUSION: This study found gadolinium enhanced MRI findings to be unreliable as an indicator for inflammation of disc herniation or nerve root in patients with sciatica.2