Reduction of angiotensin II in the cerebrospinal fluid of patients with multiple sclerosis.

We previously demonstrated that angiotensin II acts as a crucial neuroprotective factor after neural injury through angiotensin II type-2 (AT2) receptor signaling. Although the pathway is known to play an important role in the development of experimental autoimmune encephalomyelitis, cerebrospinal fluid (CSF) angiotensin II levels in patients with multiple sclerosis (MS) have never been studied. To clarify the significance of angiotensin II in MS, we assayed angiotensin II concentrations using an established enzyme-linked immunoabsorbent assay in CSF samples from patients with MS (n = 21), patients with inflammatory neuropathies (IN) (n = 23) and control individuals who did not have either of the neurological diseases or any other disease that might affect the angiotensin II levels in the CSF (control) (n = 24). Angiotensin II levels in the CSF were 3.79 +/- 1.54 pg/ml in the MS group, 5.13 +/- 2.27 pg/ml in the IN group and 6.71 +/- 2.65 pg/ml in the control group. The angiotensin II levels in the CSF of the MS group were significantly lower than in the control group (p = 0.00057). Angiotensin II concentration in the CSF tended to have a negative correlation with the Kurtzke's Expanded Disability Status Scale scores during MS relapse (p = 0.0847). These findings suggest that reduced levels of intrathecal angiotensin II may be related to the abnormal neural damage and repair processes in MS.