Analysis of IL-6, IL-1β and TNF-α production in monocytes isolated from multiple sclerosis patients treated with disease modifying drugs

Fiedler, Sarah E.; George, Joshua D; Love, Haley N.; Kim, Edward; Spain, Rebecca; Bourdette, Dennis; Salinthone, Sonemany

doi:10.15761/jsin.1000166

Cited by 19 publications

(18 citation statements)

References 29 publications

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“…In MS, increased serum concentrations of IL-6 have been reported, particularly in patients with longer disease duration (Stelmasiak et al, 2000). Moreover, enhanced IL-6 release has been documented in monocytes from MS patients (Fiedler et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

IL-6 in the Cerebrospinal Fluid Signals Disease Activity in Multiple Sclerosis

Bassi

Iezzi

Drulović

et al. 2020

Front. Cell. Neurosci.

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Specific proinflammatory and anti-inflammatory molecules could represent useful cerebrospinal fluid (CSF) biomarkers to predict the clinical course of multiple sclerosis (MS). The proinflammatory molecule interleukin (IL)-6 has been investigated in the pathophysiology of MS and has been associated in previous smaller studies to increased disability and disease activity. Here, we wanted to further address IL-6 as a possible CSF biomarker of MS by investigating its detectability in a large cohort of 534 MS patients and in 103 individuals with other non-inflammatory neurological diseases. In these newly diagnosed patients, we also explored correlations between IL-6 detectability, MS phenotypes, and disease characteristics. We found that IL-6 was more frequently detectable in the CSF of MS patients compared with their control counterparts as significant differences emerged between patients with Clinically isolated syndrome (CIS), Relapsing-remitting (RR), and secondary progressive and primary progressive MS compared to non-inflammatory controls. IL-6 was equally present in the CSF of all MS phenotypes. In RR MS patients, IL-6 detectability was found to signal clinically and/or radiologically defined disease activity, among all other clinical characteristics. Our results add further evidence that CSF proinflammatory cytokines could be useful for the identification of those MS patients who are prone to increased disease activity. In particular, IL-6 could represent an interesting prognostic biomarker of MS, as also demonstrated in other diseases where CSF IL-6 was found to identify patients with worse disease severity.

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Section: Discussionmentioning

confidence: 99%

IL-6 in the Cerebrospinal Fluid Signals Disease Activity in Multiple Sclerosis

Bassi

Iezzi

Drulović

et al. 2020

Front. Cell. Neurosci.

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“…previous data with these donors suggests disease-modifying drugs (DMDs) may have effects on cytokine response]. 15 This latter issue may also explain why the response of patients with RRMS to LA is weaker-for example, dimethyl fumarate is an RRMS drug which has both anti-inflammatory and antioxidant properties (similar to LA), and it is thus possible that its use will mask the effects of LA if they share mechanism(s) of action. LA also blocked MDM secretion of TNF-a and IL-6, but surprisingly stimulated IL-1b secretion.…”

Section: Discussionmentioning

confidence: 99%

“…For IL-6, in addition to less robust LA inhibition, LPS/IFNc polarization results in significantly higher cytokine secretion in RRMS MDM; the latter is consistent with previous studies. 15,16 Finally, LA + LPS/IFNc co-treatment results in significantly higher IL-1b levels in RRMS MDM compared with HC, perhaps as a result of the synergistic effect that is absent in HC MDM.…”

Section: La Has Mixed Effects On Inflammatory Cytokine Secretion In Mmentioning

confidence: 94%

“…Specifically, GM-CSF promotes monocyte migration across the blood-brain barrier into the central nervous system, and the LPS/IFNc polarization stimulates production of cytokines that are present at elevated levels in active MS brain lesions [tumor necrosis factor-a (TNF-a), interleukin (IL)-6 and IL-1b]. 14,15 To ensure results presented herein were not a result of cytotoxicity of these treatments, lactate dehydrogenase assays were performed on all samples, showing no significant differences between treatments (data not shown).…”

Section: Cell Culture and Polarizationmentioning

confidence: 99%

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

et al. 2020

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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.

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“…[29] [30][31].Figure 1 summarizes MS disease detection methods that have used machine learning detective models.…”

mentioning

confidence: 99%