EICOSANOID SYNTHESIS IN PERIPHERAL-BLOOD MONOCYTES - A MARKER OF DISEASE-ACTIVITY IN LUPUS NEPHRITIS

A typical feature of lupus nephritis is glomerular and interstitial le ukocyte infiltration. In search of a serological marker of renal disea se activity, we examined prostaglandin endoperoxide synthetase (PGHS) activity in peripheral-blood monocytes isolated from 5 healthy subject s and 11 untreated patients with biopsy-proven lupus nephritis, using radioimmunoassay of prostaglandin E-2 (PGE(2)) and thromboxane B-2 (Tx B(2)) released during 24-hour cultures with selective stimuli/inhibito rs. Unstimulated basal PGE(2) and TxB(2) synthesis, reflecting in vivo PGHS activity, was greater in the five patients with active renal inv olvement (World Health Organization [WHO] classes IVb-c) and the six l upus patients without active disease than in the five healthy subjects (TxB(2), 2,643 +/- 198 [standard error], 2,015 +/- 190, 1,548 +/- 295 pg/10(6) cells, respectively). Escherichia coli lipopolysaccharide (L PS; 10 mu g/mL) potently induced TxB(2) or PGE(2) synthesis in healthy controls (+255% +/- 76% and +611% +/- 190%, +688% +/- 234% and +3,189 % +/- 154%; 4 to 24 hours, respectively), an effect abolished by 5 mu mol/L of dexamethasone (DEX) or by 5 mu mol/L of the protein synthesis inhibitor cycloheximide (CHX). Responses to LPS were reduced in lupus patients without disease activity and reduced even further in those w ith active nephritis. This may be related to substrate depletion or fe edback functional inhibition of the inducible isoform of PGHS. Our ass ay may prove useful in the early detection of kidney disease activity in lupus erythematosus. (C) 1998 by the National Kidney Foundation, In c.