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Failure of anti-inflammatory steroids to inhibit prostaglandin production by rat polymorphonuclear leucocytes
Abstract:
1 Like rabbit polymorphonuclear (PMN) leucocytes, rat peritoneal glycogen-induced PMN leucocytes produced much greater amounts of prostaglandin when incubated with killed bacteria than in the absence of phagocytosable material. 2 Rat PMN leucocytes mainly prostaglandin E2 (PGE2), in amounts up to 17 ng/10(6) cells in 90 min incubation, some 25 times the amount produced by resting cells. 3 Indomethacin and meclofenamic acid inhibited prostaglandin production by resting and phagocytosing cells, the IC50 being of the order of 10(-6) to 10(-7) M for both drugs. 4 Hydrocortisone and dexamethasone at concentrations up to 10(-4) M did not cause significant dose-related inhibition of prostaglandin production in this system. 5 It is suggested that the phagocytosing PMN leucocyte is insensitive to the action of anti-inflammatory steroids with respect to prostaglandin production.
Insights
Phagocytosing rat polymorphonuclear (PMN) leucocytes produce significantly more prostaglandin E2 (PGE2) when exposed to bacteria. Anti-inflammatory steroids like hydrocortisone did not inhibit this PGE2 production in PMN leucocytes.
Area of Science:
- Immunology
- Pharmacology
Background:
- Polymorphonuclear (PMN) leucocytes play a crucial role in inflammatory responses.
- Prostaglandins, particularly prostaglandin E2 (PGE2), are key mediators of inflammation.
- The effect of phagocytosis and anti-inflammatory drugs on prostaglandin production in PMN leucocytes requires further elucidation.
Purpose of the Study:
- To investigate the production of prostaglandins by rat peritoneal glycogen-induced PMN leucocytes.
- To determine the influence of phagocytosable material (killed bacteria) on prostaglandin synthesis.
- To evaluate the inhibitory effects of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on prostaglandin production in PMN leucocytes.
Main Methods:
- Incubation of rat peritoneal PMN leucocytes with and without killed bacteria.
- Quantification of prostaglandin production using established assays.
- Assessment of the inhibitory effects of indomethacin, meclofenamic acid, hydrocortisone, and dexamethasone on prostaglandin synthesis.
Main Results:
- Phagocytosing PMN leucocytes produced significantly higher amounts of prostaglandin compared to resting cells, primarily PGE2 (up to 17 ng/10(6) cells in 90 min).
- Indomethacin and meclofenamic acid effectively inhibited prostaglandin production in both resting and phagocytosing cells, with IC50 values in the 10(-6) to 10(-7) M range.
- Hydrocortisone and dexamethasone did not exhibit significant dose-related inhibition of prostaglandin production at concentrations up to 10(-4) M.
Conclusions:
- Phagocytosis by PMN leucocytes markedly enhances prostaglandin production.
- NSAIDs are effective inhibitors of prostaglandin synthesis in PMN leucocytes.
- Phagocytosing PMN leucocytes appear to be insensitive to the inhibitory effects of commonly used anti-inflammatory steroids regarding prostaglandin production.