IL-18 and IL-18BP in Amyotrophic Lateral Sclerosis
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1
National Research Council, Italy
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2
University of Pisa, Internal Medicine, Italy
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3
University of Pisa, Neuroscience, Italy
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4
University of Brescia, Neurology, Italy
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5
IRCCS Fondazione Santa Lucia, Clinical and Behavioral Neurology, Italy
The role of inflammation in neurodegenerative diseases, included ALS, is increasingly recognized. Activation of caspase-1 has been demonstrated in the spinal cord of ALS mice and humans. To investigate if inflammasome hyperactivation is pathogenic, promoting neuroinflammation and contributing to ALS progression, we analyzed the levels of IL-18 and IL-18BP in serum and CSF from ALS patients.
Serum and CSF samples were collected from 103 patients with sALS. A control group consisted of 40 healthy serum donors; a second group included 69 CSF donors, either healthy or with different kinds of non-infectious non-inflammatory diseases. Cytokine levels were measured by ELISA. The levels of free IL-18 were calculated by the law of mass action.
Levels of IL-18 (21.99±14.03 pM), IL-18BP (471.54±230.50 pM) and free IL-18 (9.92±5.21 pM) were significantly higher in ALS serum than in healthy controls (IL-18: 12.12±7.24 pM, p<0.0001; IL-18BP: 268.83±165.85 pM, p<0.0001; free IL-18: 7.35±4.02 pM, p=0.0006). No correlation between cytokine levels and disease stage was found. IL-18 was undetectable in CSF, while IL-18BP was found at significant and comparable levels in both ALS patients and controls.
High circulating IL-18 concentrations may suggest the involvement of inflammasome-dependent inflammation in the disease, but the lack of correlation between IL-18 levels and disease stage suggests that the cytokine is not involved in triggering the disease exacerbation. The abundant presence of IL-18BP in the CSF in the absence of its cytokine target may imply the physiological need of maintaining homeostasis in a fundamental organ like the brain.
Keywords:
Inflammation,
Amyotrophic lateral sclerosis (ALS),
Cytokines,
Inflammasome,
Neurodegenerative Diseases
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Giungato
P,
Italiani
P,
Migliorini
P,
Siciliano
G,
Borroni
B,
Bossu'
P and
Boraschi
D
(2013). IL-18 and IL-18BP in Amyotrophic Lateral Sclerosis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00133
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Received:
11 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Miss. Paola Giungato, National Research Council, Pisa, Italy, paolagiungato@gmail.com
Dr. Diana Boraschi, National Research Council, Pisa, Italy, diana.boraschi@gmail.com