Enhanced gastric mucosal leukotriene B4 synthesis in patients taking non-steroidal anti-inflammatory drugs.
The effects of longstanding non-steroidal anti-inflammatory drug (NSAID) treatment on gastric mucosal synthesis of leukotriene B4 (LTB4), leukotriene C4 (LTC4), and prostaglandin E2 (PGE2) was studied. Gastric antral biopsies in 65 patients with arthritis taking NSAIDs and 23 control patients were taken and eicosanoid concentrations, stimulated by vortex mixing or calcium ionophore, were measured by radioimmunoassay. Median gastric mucosal synthesis of LTB4 was increased in patients taking NSAIDs compared with non-users: (0.9(0.2-2.5) pg/mg v 0 (0-0.6) pg/mg (p < 0.001)). These differences persisted when subgroups of patients were analysed according to Helicobacter pylori colonisation or degree of mucosal injury. Synthesis of LTB4 was strongly associated with the presence of type C (chemical) gastritis. Increased synthesis of LTC4 was associated with Helicobacter pylori colonisation but not NSAID use. Synthesis of PGE2 was decreased in patients taking NSAIDs compared with control patients (p < 0.001). Enhanced gastric mucosal synthesis of LTB4 in patients taking NSAIDs may represent a primary effect of these drugs and could be implicated in the pathogenesis of gastritis and ulceration associated with NSAIDs.
Department of Medicine, University Hospital, Nottingham.
N
N
Hudson
M
M
Balsitis
S
S
Everitt
C J
CJ
Hawkey
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005756:Gastritis / Q000139:chemically induced / Q000378:metabolism; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D013189:SRS-A / Q000096:biosynthesis; D013276:Stomach Ulcer / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013189:SRS-A; D007975:Leukotriene B4; D015232:Dinoprostone