INCREASED SOLUBLE ENDOTHELIAL ADHESION MOLECULES IN RHEUMATOID-ARTHRITIS CORRELATE WITH CIRCULATING CYTOKINES AND DEPLETION OF CD45RO(-LYMPHOCYTES FROM BLOOD-STREAM() T)

Endothelial cells express adhesion molecules and release free forms (e .g., sELAM-1, sGMP-140, sICAM-1 and sVCAM-1). Compared with controls, the serum levels of these soluble adhesion molecules (SAM) were signif icantly increased in patients with rheumatoid arthritis. We investigat ed whether this was associated with the circulating cytokines and chan ges in peripheral blood T-lymphocyte (T-PBL) subsets. In healthy subje cts, sELAM-1 correlated with the serum levels of Il-1 beta, Il-1 recep tor antagonist (Il-1RA) and Il-6, while sGMP-140 was associated with I l-8, and sVCAM-1 was related to Il-7 and Il-8. Thus, already in contro ls, relations exist between the levels of SAM and circulating cytokine s. The rheumatoid arthritis patients with low and high serum levels of IgA- and/or IgM-rheumatoid factors (RF) were separately analyzed. The y have different cytokine profiles and showed distinct correlations. I n patients with low RF, sGMP-140 and sVCAM-1 correlated with Il-1 beta , while sICAM-1 was associated with Il-7 and TNF-alpha. In patients wi th high RF, sELAM-1 correlated with Il-1RA, and sGMP-130 was associate d with many cytokines (e.g., GM-CSF, MIP-1a and TNF-alpha). In additio n, lymphopenia (less than 1000 lymphocytes/mu l) was shown in 30% of t he patients, and 20% (mostly with low RF levels) had reduced levels of ''primed'' CD45RO(+) cells among T-PBL. In controls, cytokines (Il-7, Il-8 and GM-CSF), but not SAM, were associated with less CD45RO(+) T- PBL. In patients with low RF only, sGMP-140 and sELAM-1 correlated wit h the depletion of ''primed'' CD4(+) and CD8(+) T-PBL respectively. In such patients, Il-1 beta and GM-CSF also correlated with less CD8(+), CD45RO(+) T-PBL. Thus, particularly in patients with low RF, increase d SAM, possibly released by the endothelial cells, might reflect the c ytokine-induced activation of the vascular endothelium and the extrava sation of some CD45RO(+) T-PBL.