Endothelin-1 is elevated in the cerebrospinal fluid of HIV-infected patients with encephalopathy

In a cross-sectional, non-randomized, prospective study in an outpatient clinic a possible relationship between the cerebrospinal fluid (CSF) concentrations of the potent vasoconstrictor peptide endothelin-1 (ET-1) and prevalence and degree of HIV-encephalopathy was studied. Forty-eight CSF samples from HIV-infected patients undergoing lumbar punction for diagnostic reasons were investigated for ET-1 concentrations. In 37 patients ET-1 was also measured in plasma. Patients were investigated clinically and staged with respect to HIV encephalopathy. Patients with arterial hypertension, diabetes or acute opportunistic infections were excluded from the study. In the remaining, 18 of the CSF samples were from patients with normal neurological findings (grade 0-0.5), whereas 30 were from patients with HIV encephalopathy (grade 1-3). The mean CSF ET-1 concentration was significantly elevated (P = 0.001) in patients with HIV encephalopathy (1.97 +/- 2.33 pmol/l) as compared to those patients without encephalopathy (0.57 +/- 0.67 pmol/l). Moreover, there was a significant correlation between ET-1 CSF concentrations and the degree of HIV encephalopathy (r = 0.49, P < 0.001). In addition, there was a significant correlation between ET-1 levels in the CSF and the IgG serum to CSF ratio. However, we found no correlation between HIV encephalopathy and neither CSF total protein, IgG, albumin or the serum to CSF ratio of IgG or albumin. In conclusion, we could demonstrate a close relationship between CSF ET-1 concentrations and the degree of HIV encephalopathy. Thus, by virtue of its long-lasting and potent vasoconstrictor activity ET-1 might contribute to the pathogenesis of HIV encephalopathy.