Biomaterial Database

Inhibitory effects of diclofenac and indomethacin on interleukin-1-induced changes in PGE2 release. A novel effect on free arachidonic acid levels in human synovial cells. 1989

L A O'Neill, and G P Lewis

Department of Pharmacology, Royal College of Surgeons, London, U.K.

The inhibitory effects of two non-steroidal anti-inflammatory drugs (NSAIDS), diclofenac and indomethacin, on interleukin-1 (IL-1)-induced changes in arachidonic acid (AA) release and prostaglandin E2(PGE2) production by human synovial cells was investigated. Both diclofenac and indomethacin potently inhibited IL-1 alpha-induced PGE2 release, with IC50 values of 1.6 +/- 0.02 nM and 5.5 +/- 0.1 nM, respectively. A novel effect on IL-1 alpha-mediated changes in AA levels was observed using cells labelled with radioactive AA. Both drugs at micromolar concentrations (10-30 microM) showed an apparent inhibition of IL-1 alpha-induced increases in radioactivity associated with free AA. Concomitant with this inhibition, there was an increase in radioactivity associated with phosphatidylethanolamine (PE) and triglyceride (TG). As the drugs had no effect on IL-1 alpha-induced decreases in radioactivity associated with phosphatidylcholine (PC), this result was interpreted as being due to an enhanced acylation of AA into PE and TG. These results suggest that whilst at nanomolar concentrations, diclofenac and indomethacin can inhibit IL-1 alpha-induced PGE2 output, at micromolar concentrations an effect on free AA levels is also evident. This may have consequences for the release of other mediators such as leukotrienes, whose synthesis also involves the level of free AA.

UI	MeSH Term	Description	Entries
D007213	Indomethacin	A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.	Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004008	Diclofenac	A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.	Diclophenac,Dichlofenal,Diclofenac Potassium,Diclofenac Sodium,Diclonate P,Dicrofenac,Feloran,GP-45,840,Novapirina,Orthofen,Orthophen,Ortofen,SR-38,Sodium Diclofenac,Voltaren,Voltarol,Diclofenac, Sodium,GP 45,840,GP45,840,SR 38,SR38
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000210	Acute-Phase Reaction	An early local inflammatory reaction to insult or injury that consists of fever, an increase in inflammatory humoral factors, and an increased synthesis by hepatocytes of a number of proteins or glycoproteins usually found in the plasma.	Acute Phase Response,Acute-Phase State,Reaction, Acute-Phase,Response, Acute-Phase,Acute Phase Reaction,Acute Phase Responses,Acute Phase State,Acute-Phase Response,Phase Response, Acute,Reaction, Acute Phase,Response, Acute Phase,State, Acute-Phase
D001095	Arachidonic Acids		Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic
D013583	Synovial Membrane	The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes SYNOVIAL FLUID.	Synovium,Membrana Synovialis Capsulae Articularis,Membrane, Synovial,Membranes, Synovial,Synovial Membranes
D015232	Dinoprostone	The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.	PGE2,PGE2alpha,Prostaglandin E2,Prostaglandin E2alpha,PGE2 alpha,Prepidil Gel,Prostaglandin E2 alpha,Prostenon,E2 alpha, Prostaglandin,E2, Prostaglandin,E2alpha, Prostaglandin,Gel, Prepidil,alpha, PGE2,alpha, Prostaglandin E2
D016718	Arachidonic Acid	An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.	(all-Z)-5,8,11,14-Eicosatetraenoic acid,Arachidonic Acid, (all-Z)-Isomer, 1-(14)C-Labeled,Arachidonic Acid, (all-Z)-isomer, 3H-Labeled,Arachidonic Acid, Ammonium Salt, (all-Z)-Isomer,Arachidonic Acid, Cerium Salt, (all-Z)-Isomer,Arachidonic Acid, Cesium Salt, (all-Z)-Isomer,Arachidonic Acid, Lithium Salt, (all-Z)-Isomer,Arachidonic Acid, Potassium Salt, (all-Z)-Isomer,Arachidonic Acid, Sodium Salt,Arachidonic Acid, Sodium Salt, (all-Z)-Isomer,Arachidonic Acid, Zinc Salt, (all-Z)-Isomer,Sodium Arachidonate,Vitamin F,Arachidonate, Sodium