Elevated Soluble IL-2 Receptor in CSF and Blood: Clinical Significance
Elevated soluble Interleukin-2 receptor (sIL-2R) levels in cerebrospinal fluid (CSF) and blood primarily indicate the presence of activated T-lymphocytes and inflammatory processes within the central nervous system, which can occur in various neurological disorders including multiple sclerosis, neurosarcoidosis, meningeal infiltration in hematological malignancies, and other inflammatory neurological conditions.
General Significance of Elevated sIL-2R
- Elevated sIL-2R in CSF indicates the presence of activated T-lymphocytes within the central nervous system, suggesting an inflammatory process 1
- sIL-2R is part of a complex network of inflammatory markers and should not be interpreted in isolation, as a single inflammatory marker is insufficient to describe an entire biological cascade 2
- The interpretation of elevated sIL-2R should consider the context-dependent functions of inflammatory markers, which can vary based on location (perivascular space vs. interstitial space) and pathological state 2
Clinical Conditions Associated with Elevated sIL-2R
- Multiple Sclerosis (MS): Significantly increased CSF IL-2R levels are observed in MS patients, with this group showing the highest values compared to other neurological disorders 1
- Neurosarcoidosis: CSF sIL-2R levels above 150 pg/ml can identify untreated neurosarcoidosis with 93% accuracy when compared to non-infectious CNS diseases 3
- Meningeal Infiltration in Hematological Malignancies:
- Subarachnoid Hemorrhage: Moderate increases in soluble IL-2R are detected in the CSF of patients following subarachnoid hemorrhage 5
- Aseptic Meningitis: Significant increases in CSF IL-2R levels are observed 1
- Lymphoid CNS Tumors: Significant increases in CSF IL-2R levels are observed 1
Interpretation Considerations
- CSF sIL-2R levels do not necessarily correlate with serum sIL-2R levels, suggesting independent intrathecal synthesis rather than passive transfer across the blood-brain barrier 5
- In ATL patients with meningeal infiltration, CSF sIL-2R levels tend to correlate with numbers of mononuclear cells and lactic dehydrogenase (LDH) in CSF, but not with serum sIL-2R levels 4
- Pro-inflammatory markers like sIL-2R are not inherently "bad," and their interpretation should consider their pleiotropic nature at different concentrations 2
- Inflammatory markers should be evaluated as part of a network-based approach rather than in isolation 2
Important Caveats
- CSF inflammatory markers may show nonlinear or U-shaped trajectories in aging and disease progression, making single threshold-crossing impractical 2
- The presence of co-pathologies, especially in older individuals, can complicate the interpretation of inflammatory markers 2
- Inflammatory markers in CSF should not be used to infer specific cellular changes based solely on experimental data from blood or in vitro studies 2
- Parenchymal glia secretome may be insufficiently and non-uniformly captured by bulk CSF assays, limiting direct correlations between CSF markers and brain pathology 2
Recommended Approach to Interpretation
- Consider measuring multiple inflammatory markers simultaneously to capture the complexity of neuroinflammatory processes 2
- Interpret sIL-2R levels in the context of the specific clinical presentation and other laboratory findings 2
- Recognize that elevated sIL-2R may indicate different processes depending on the underlying condition 2
- Consider the time-dependent, region-dependent, and disease context-dependent nature of neuroinflammation when interpreting results 2