Related Experiment Videos
The hypothalamo-pituitary-adrenal axis in multiple sclerosis
Inge Huitinga1, Zeynel A Erkut, Denis van Beurden
1Netherlands Institute for Brain Research, Amsterdam, The Netherlands. i.huitinga@nih.knaw/nl
Annals of the New York Academy of Sciences
|June 10, 2003
Summary
Multiple sclerosis (MS) patients show activated hypothalamo-pituitary-adrenal (HPA) axis, but hypothalamic lesions impair this response, worsening disease course. This suggests hypothalamic MS lesions negatively impact HPA axis function and recovery.
Area of Science:
- Neuroimmunology
- Endocrinology
- Neuropathology
Background:
- The hypothalamo-pituitary-adrenal (HPA) axis modulates immune responses, potentially aiding recovery from multiple sclerosis (MS) relapses.
- MS is characterized by inflammation and demyelination in the central nervous system (CNS).
- Previous studies indicated HPA axis activation in MS patients.
Purpose of the Study:
- To investigate the role of chronic CNS inflammation in HPA axis activation in MS.
- To determine if interleukin-6 (IL-6) in cerebrospinal fluid (CSF) drives HPA axis activation in MS.
- To examine the impact of hypothalamic MS lesions on HPA axis function and disease course.
Main Methods:
- Postmortem analysis of HPA axis markers (CRH neurons, cortisol) in MS patients and controls.
- Quantification of MS lesions in the hypothalamus and IL-6 levels in CSF.
- Correlation analysis between HPA axis markers, IL-6, and clinical data (disease duration).
Main Results:
- MS patients exhibited activated HPA axis (elevated CRH neurons, CSF cortisol) but blunted cortisol response to sepsis.
- CSF IL-6 levels did not differ between MS and control groups; IL-6 did not correlate with cortisol in MS.
- A high incidence (95%) of hypothalamic MS lesions was observed, with active lesions correlating with shorter disease duration.
- Active hypothalamic lesions appeared to suppress CRH neuron activation.
Conclusions:
- The activated HPA axis in MS is unresponsive to acute inflammatory stimuli like sepsis.
- IL-6 in CSF is not the cause of HPA axis activation in MS.
- Active hypothalamic MS lesions are prevalent, associated with a worse disease course, and may suppress CRH neurons, leading to inadequate cortisol response during relapses.