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Increased release of interleukin-12p40 in MS: association with intracerebral inflammation
K Fassbender1, A Ragoschke, S Rossol
1Department of Neurology, University of Heidelberg, Klinikum Mannheim, Germany.
Objective:
The p40 subunit of interleukin (IL)-12 was recently demonstrated in active lesions in MS. We tested whether the p40 subunit of IL-12 can also be detected in CSF and serum of patients with this disease and, if so, whether release is associated with inflammatory disease activity.
Results:
This study demonstrates an increased (up to 1,000-fold) compartmentalized release of the p40 subunit but not of the heterodimer p70 in MS. Release of IL-12p40 correlated with classic markers of CNS inflammation (CSF cell counts, immunoglobulin G index) and was significantly increased in patients with gadolinium-enhancing plaques on MRI. Moreover, release of IL-12p40 was associated with CSF levels of myelin basic protein as a measure of myelin degradation.
Conclusion:
These results suggest a role of IL-12p40 in the pathophysiology of MS.
Insights
Interleukin-12 (IL-12) p40 subunit is elevated in cerebrospinal fluid and serum of multiple sclerosis (MS) patients, correlating with disease activity and myelin damage.
Area of Science:
- Neuroimmunology
- Inflammatory Diseases
Background:
- The p40 subunit of interleukin-12 (IL-12) has been observed in active lesions associated with multiple sclerosis (MS).
- The presence and significance of IL-12p40 in the cerebrospinal fluid (CSF) and serum of MS patients require further investigation.
Purpose of the Study:
- To determine if the IL-12 p40 subunit is detectable in the CSF and serum of MS patients.
- To investigate the association between IL-12p40 release and inflammatory disease activity in MS.
Main Methods:
- Analysis of IL-12 p40 subunit levels in CSF and serum of MS patients.
- Correlation of IL-12p40 levels with established markers of central nervous system (CNS) inflammation, including CSF cell counts and immunoglobulin G index.
- Assessment of IL-12p40 levels in relation to MRI findings (gadolinium-enhancing plaques) and myelin degradation (myelin basic protein levels).
Main Results:
- A significant, compartmentalized increase (up to 1,000-fold) in IL-12p40 release was observed in MS patients, whereas the IL-12p70 heterodimer was not detected.
- IL-12p40 release strongly correlated with markers of CNS inflammation, such as elevated CSF cell counts and immunoglobulin G index.
- Increased IL-12p40 levels were significantly associated with the presence of gadolinium-enhancing lesions on MRI and with higher CSF levels of myelin basic protein, indicating myelin degradation.
Conclusions:
- The findings suggest a significant role for IL-12p40 in the inflammatory processes and pathophysiology of multiple sclerosis.
- Elevated IL-12p40 may serve as a potential biomarker for active inflammation and myelin damage in MS.