Increased serum levels of TNF-α and decreased serum levels of IL-27 in patients with Parkinson disease and their correlation with disease severity

Kouchaki, Ebrahim; Kakhaki, Reza Daneshvar; Tamtaji, Omid Reza; Dadgostar, Ehsan; Behnam, Mohammad; Nikoueinejad, Hassan; Akbari, Hossein

doi:10.1016/j.clineuro.2018.01.022

Cited by 60 publications

(54 citation statements)

References 39 publications

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“…As in several other neurological disease, increased levels of TNF and sTNF(R1) are evident in the CSF and tissues of PD patients, as well as in postmortem brain tissue. The levels found in serum correlated with disease severity according to some researchers [118,224]. One group also found that TNF gene promoter polymorphism were associated with an earlier age of PD onset [225].…”

Section: Tnf In Parkinson's Diseasementioning

confidence: 90%

A New Venue of TNF Targeting

Steeland

Libert

Vandenbroucke

2018

Preprint

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The first FDA-approved drugs were small, chemically-manufactured and highly active molecules with possible off-target effects. After this first successful wave of small drugs, biotechnology allowed the development of protein-based medicines such as antibodies. Conventional antibodies bind a specific protein and are becoming increasingly important in the therapeutic landscape. A very prominent class of biologicals are the anti-TNF drugs that are applied in several inflammatory diseases that are characterized by dysregulated TNF levels. Marketing of TNF inhibitors revolutionized the treatment of diseases such as Crohn’s disease. However, these inhibitors also have undesired effects, some of them directly associated with the inherent nature of this drug class such as immunogenicity, whereas others are linked with their mechanism of action. Recently, researchers tried to design innovative drugs with reduced side effects aiming to make them more effective and safer. Molecules with more specificity e.g. that target one specific TNF format or receptor, or that neutralize the TNF signaling pathway in specific cells, are generated. Alternatively, TNF-directed biologicals without the typical antibody structure are manufactured. Here, we review the complications related to the use of conventional TNF inhibitors, together with the anti-TNF alternatives and the different (neurodegenerative) diseases that might benefit from selective approaches.

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Section: Tnf In Parkinson's Diseasementioning

confidence: 90%

A New Venue of TNF Targeting

Steeland

Libert

Vandenbroucke

2018

Preprint

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“…Accumulating evidence reveals a pivotal role of chronic neuroinflammation on the pathologic features of PD(Collins et al, 2012). Inflammatory mediators, such as NO, TNF-α, IL-1β, and IL-6 may contribute to the progression of PD (Niranjan et al, 2012; Williams-Gray et al, 2016; Kouchaki et al, 2018). This study showed that the PD-TD group had a significantly elevated IL-6 level in the CSF when compared with the PD-PIGD and control groups (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Tremor-Dominant in Parkinson Disease: The Relevance to Iron Metabolism and Inflammation

et al. 2019

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Background: Tremor is one of the most predominant symptoms of patients with Parkinson disease (PD), but the underlying mechanisms for tremor relating to iron and its metabolism-related proteins and the inflammatory factors in cerebrospinal fluid (CSF) and serum have not been fully elucidated. Methods: A total of 135 PD patients were divided into a tremor-dominant (PD-TD) group ( N = 74) and a postural instability and gait difficulty-dominant (PD-PIGD) group ( N = 39) based on the ratio of mean tremor score to the mean bradykinesia/rigid score of the Unified Parkinson’s Disease Rating Scale (UPDRS) III. Age and sex-matched healthy controls were recruited ( N = 35). Demographic variables were evaluated; iron and its metabolism-related proteins and the inflammatory mediators in both CSF and serum were measured in these groups. The relevance of iron metabolism, inflammation and PD-TD were analyzed. Results: (1) The PD-TD group had significantly decreased L -ferritin, increased iron levels in CSF and increased ferritin levels in the serum compared with the PD-PIGD and control groups ( P < 0.05). (2) The PD-TD group had significantly enhanced IL-6 levels in both CSF and serum compared with the PD-PIGD and control groups ( P < 0.05). (3) In CSF, the IL-6 level was increased as the iron level was elevated in the PD-TD group ( r = 0.308, P = 0.022). In serum, the IL-6 level was increased as the ferritin level was elevated in the PD-TD group ( r = 0.410, P = 0.004). Conclusion: The interplay between disturbed iron metabolism and relevant inflammation might modulate clinical phenotypes of PD.

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“…As in several other neurological disease, increased levels of TNF and sTNF(R1) are evident in the CSF and tissues of PD patients, as well as in postmortem brain tissue. The levels found in serum correlated with disease severity according to some researchers [ 124 , 233 ]. One group also found that TNF gene promoter polymorphisms were associated with an earlier age of PD onset [ 234 ].…”

Section: Tnf In Health and Diseasementioning

confidence: 84%

A New Venue of TNF Targeting

Steeland

Libert

Vandenbroucke

2018

IJMS

104

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The first Food and Drug Administration-(FDA)-approved drugs were small, chemically-manufactured and highly active molecules with possible off-target effects, followed by protein-based medicines such as antibodies. Conventional antibodies bind a specific protein and are becoming increasingly important in the therapeutic landscape. A very prominent class of biologicals are the anti-tumor necrosis factor (TNF) drugs that are applied in several inflammatory diseases that are characterized by dysregulated TNF levels. Marketing of TNF inhibitors revolutionized the treatment of diseases such as Crohn’s disease. However, these inhibitors also have undesired effects, some of them directly associated with the inherent nature of this drug class, whereas others are linked with their mechanism of action, being pan-TNF inhibition. The effects of TNF can diverge at the level of TNF format or receptor, and we discuss the consequences of this in sepsis, autoimmunity and neurodegeneration. Recently, researchers tried to design drugs with reduced side effects. These include molecules with more specificity targeting one specific TNF format or receptor, or that neutralize TNF in specific cells. Alternatively, TNF-directed biologicals without the typical antibody structure are manufactured. Here, we review the complications related to the use of conventional TNF inhibitors, together with the anti-TNF alternatives and the benefits of selective approaches in different diseases.

show abstract

Increased serum levels of TNF-α and decreased serum levels of IL-27 in patients with Parkinson disease and their correlation with disease severity

Cited by 60 publications

References 39 publications

A New Venue of TNF Targeting

A New Venue of TNF Targeting

Tremor-Dominant in Parkinson Disease: The Relevance to Iron Metabolism and Inflammation

A New Venue of TNF Targeting

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