Researchers evaluate the use of inflammatory molecules as potential biomarkers for amyotrophic lateral sclerosis

Written by Sarah Jones, Future Science Group

Findings from a recent study have identified pro-inflammatory molecules as potential diagnostic markers for amyotrophic lateral sclerosis (ALS), as increased levels of pro-inflammatory molecules have been found in the blood of ALS patients. The fatal neurodegenerative disease, ALS, is characterized by progressive degeneration of neurones in the brain and spinal cord. Currently, the disease has no effective therapies, with research focusing on elucidating the cause.

It has been suggested by numerous studies that inflammation in the central nervous system plays a key role in ALS. More specifically, levels of immune cells in the central nervous system have been demonstrated to be increased in ALS patients. Clinical studies have also pointed to a role of peripheral inflammation in ALS, with markers of inflammation such as T-cells, cytokines and chemokines being found in patients with the disease.

However, the accumulated research focusing on peripheral cytokines is contradictory. Some studies have shown increases in pro-inflammatory cytokines and chemokines in the blood, whereas others have reported levels similar to controls.

In an effort to make sense of these contradictory results, the authors of this new study carried out a systematic review of published research reporting on levels of inflammatory cytokines in ALS patients and controls. A total of 25 studies were combined and analyzed, involving 812 ALS patients and 639 controls.

It was demonstrated, in  this review, specific evidence that levels of pro-inflammatory TNF-alpha, TNF receptor 1, IL-6, IL-1beta, IL-8 and vascular endothelial growth factor were significantly elevated in the blood of patients in ALS when compared with controls. It was also demonstrated, contradictory to previous reports, that other cytokines and proteins, including the chemokine monocyte chemotactic protein, were not elevated.

These results should be interpreted with caution, however, as the authors noted that ‘a single study could influence the statistically significant differences in blood IL-1beta, IL-6 and VEGF levels between ALS patients and control subjects’. Therefore, future studies are required to further clarify the issue.

The authors state that the findings ‘strengthen the clinical evidence of an increased inflammatory response in patients with ALS’. The potential for peripheral levels of cytokines to be utilized as biomarkers for ALS, highlighted by this study, presents a possible approach for researchers seeking to link together diagnosis and the onset of symptoms.

Sources: Hu Y, Cao C, Qin X-Y, Yu Y, Yuan J, Zhao Y, Cheng Y. Increased peripheral blood inflammatory cytokine levels in amyotrophic lateral sclerosis: a meta-analysis study. Rep. doi:10.1038/s41598-017-09097-1 (2017);