Platelet activating factor is elevated in cerebral spinal fluid and plasmaof patients with relapsing-remitting multiple sclerosis

Platelet-activating factor (PAF) is a phospholipid mediator of inflammation with a wide range of biological activities, including the alteration of ba rrier function of endothelium. A biological assay combined with high pressu re liquid chromatography-tandem mass spectrometry showed that plasma and ce rebral spinal fluid (CSF) PAF levels in 20 patients with relapsing/remittin g or secondary progressive multiple sclerosis (MS) studied by magnetic reso nance imaging (MRI) were significantly higher than in healthy controls (pla sma: 3.29 +/- 4.52 vs. 0.48 +/- 0.36 ng/ml, p < 0.002; CSF: 4.95 +/- 6.22 n g/ml vs. 0.01 +/- 0.04 ng/ml, p < 0.0001). Values were also significantly h igher in relapsing/remitting than in secondary progressive (plasma: 5.10 +/ - 4.97 vs. 0.52 +/- 0.85 ng/ml, p < 0.005; CSF: 8.59 +/- 6.39 vs. 0.55 +/- 0.68 ng/ml, p < 0.002). It was also found that both plasma (R-2: 0.65) and CSF (R-2: 0.72) levels were correlated with the MRI number of gadolinium en hancing lesions, which are markers of blood-brain barrier (BBB) injury, whe reas their peaks were not correlated with the MRI number of white matter le sions, nor with the expanded disability status score (EDSS) according to Ku rtze [Kurtze, J.F., 1983. Rating neurological impairment in multiple sclero sis: an expanded disability scale (EDSS). Neurology 33, 1444-1452]. Both pl asma and CSF in patients with relapsing/remitting MS and marked gadolinium enhancement contained the two major molecular species of PAF: 1-0-hexadecyl - (C16:O) and 1-0-octadecyl-sn-glycero-3-phosphocholine (C18:O). The ratio of the two molecular species was different in the two biological fluids, be ing PAF C18:0 more abundant in CSF and PAF C16:0 in plasma, indicating a di fferent cellular origin of PAF or different enzymatic processing. These fin dings suggest that PAF is a significant mediator of BBB injury in the early stages of MS, rather than a marker of its progression and severity. (C) 19 99 Elsevier Science B.V. All rights reserved.