A typical feature of lupus nephritis is glomerular and interstitial leukocyte infiltration. In search of a serological marker of renal disease activity, we examined prostaglandin endoperoxide synthetase (PGHS) activity in peripheral-blood monocytes isolated from 5 healthy subjects and 11 untreated patients with biopsy-proven lupus nephritis, using radioimmunoassay of prostaglandin E-2 (PGE(2)) and thromboxane B-2 (TxB(2)) released during 24-hour cultures with selective stimuli/inhibitors. Unstimulated basal PGE(2) and TxB(2) synthesis, reflecting in vivo PGHS activity, was greater in the five patients with active renal involvement (World Health Organization [WHO] classes IVb-c) and the six lupus 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 (LPS; 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 with active nephritis. This may be related to substrate depletion or feedback functional inhibition of the inducible isoform of PGHS. Our assay may prove useful in the early detection of kidney disease activity in lupus erythematosus. (C) 1998 by the National Kidney Foundation, Inc.
Eicosanoid synthesis in peripheral blood monocytes: A marker of disease activity in lupus nephritis / Mene', Paolo; Pecci, Gabriella; Cinotti, Giulio Alberto; Pugliese, Giuseppe; F., Pricci; Pugliese, Francesco. - In: AMERICAN JOURNAL OF KIDNEY DISEASES. - ISSN 0272-6386. - 32:5(1998), pp. 778-784. (Intervento presentato al convegno 29th Annual Meeting of the American-Society-of-Nephrology tenutosi a NEW ORLEANS, LOUISIANA nel NOV 03-06, 1996) [10.1016/s0272-6386(98)70133-7].
Eicosanoid synthesis in peripheral blood monocytes: A marker of disease activity in lupus nephritis
MENE', Paolo;PECCI, Gabriella;CINOTTI, Giulio Alberto;PUGLIESE, Giuseppe;PUGLIESE, Francesco
1998
Abstract
A typical feature of lupus nephritis is glomerular and interstitial leukocyte infiltration. In search of a serological marker of renal disease activity, we examined prostaglandin endoperoxide synthetase (PGHS) activity in peripheral-blood monocytes isolated from 5 healthy subjects and 11 untreated patients with biopsy-proven lupus nephritis, using radioimmunoassay of prostaglandin E-2 (PGE(2)) and thromboxane B-2 (TxB(2)) released during 24-hour cultures with selective stimuli/inhibitors. Unstimulated basal PGE(2) and TxB(2) synthesis, reflecting in vivo PGHS activity, was greater in the five patients with active renal involvement (World Health Organization [WHO] classes IVb-c) and the six lupus 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 (LPS; 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 with active nephritis. This may be related to substrate depletion or feedback functional inhibition of the inducible isoform of PGHS. Our assay may prove useful in the early detection of kidney disease activity in lupus erythematosus. (C) 1998 by the National Kidney Foundation, Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.