The cyclo-oxygenase inhibitor, piroxicam, enhances cytokine-induced lymphocyte proliferation in vitro and in vivo.
The effects of Piroxicam on the production and activity of lymphoproliferative cytokines (LC) produced by mononuclear phagocytes (MNP) were examined. In vitro, Piroxicam did not affect IL-1 induced thymocyte proliferation (LAF assay). However, the LAF activity from lipopolysaccharide (LPS)-treated MNP cultures was increased after Piroxicam (0.1-20 mumol/L) treatment. The increase in apparent LC activity was largely due to suppression of prostaglandin E2 (PGE2) production. Peripheral blood, spleen and thymus lymphocytes from animals predosed with Piroxicam (5 mg/kg per day for 3 days) synthesized more DNA than untreated mice (as measured by [3H]-thymidine uptake ex vivo). MNP from Piroxicam-treated animals produced significantly more LC. Piroxicam had similar effects in both inflamed and non-inflamed mice. Piroxicam and other non-steroidal anti-inflammatory drugs (NSAID) may therefore stimulate or modulate the immune functions requiring lymphoproliferation by suppressing the formation of PGE2, a natural inhibitor of both LC production and LC-induced lymphoproliferation.
Haynes
D R
DR
Department of Pathology, University of Adelaide, SA.
Wright
P F
PF
Whitehouse
M W
MW
Vernon-Roberts
B
B
D000818:Animals; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005233:Fatty Alcohols; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D010894:Piroxicam / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D005233:Fatty Alcohols; D010894:Piroxicam; C010268:oleyl alcohol; D004247:DNA; D015232:Dinoprostone