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The pharmacology of arachidonic acid-induced rat PMN leukocyte infiltration
M J DiMartino1, C E Wolff, G K Campbell
1Smith Kline & French Laboratories, King of Prussia, PA 19406-0939.
Abstract:
Arachidonic Acid (AA) injected into a hindpaw of Lewis rats produces high levels of tissue myeloperoxidase (MPO), a biochemical marker for PMN leukocytes. Treatment with a corticosteroid (prednisolone) or dual 5-LO/CO inhibitors of AA metabolism (phenidone, SKF 86002) produced dose-related inhibition of AA-induced elevations in paw tissue MPO levels. In contrast, administration of high pharmacologic doses of selective cyclooxygenase inhibitors (indomethacin, ibuprofen, naproxen), anti-histamine/serotonin agents (cyproheptadine, chlorpheniramine) or an anti-arthritic gold compound (auranofin) produced only slight or moderate effects. Thus, AA-induced hindpaw inflammation is a useful method for determining pharmacologic effects of 5-LO/CO inhibitors on PMN leukocyte infiltration in vivo.
Insights
Arachidonic acid-induced inflammation in rat paws effectively measures the impact of 5-lipoxygenase/cyclooxygenase inhibitors on neutrophil infiltration. Corticosteroids and dual inhibitors significantly reduced myeloperoxidase levels.
Area of Science:
- Pharmacology
- Inflammation Research
- Immunology
Background:
- Arachidonic acid (AA) injection in rat hindpaws induces significant myeloperoxidase (MPO) levels, a marker of neutrophil (PMN leukocyte) infiltration.
- Investigating the role of AA metabolism in inflammation is crucial for understanding inflammatory pathways.
Purpose of the Study:
- To evaluate the efficacy of various pharmacological agents in modulating AA-induced hindpaw inflammation.
- To determine the effectiveness of 5-lipoxygenase (5-LO) and cyclooxygenase (CO) inhibitors in reducing PMN leukocyte infiltration in vivo.
Main Methods:
- Arachidonic acid was injected into the hindpaw of Lewis rats to induce inflammation.
- Animals were treated with corticosteroids, dual 5-LO/CO inhibitors, selective cyclooxygenase inhibitors, anti-histamine/serotonin agents, or gold compounds.
- Myeloperoxidase (MPO) levels in paw tissue were measured as an indicator of PMN leukocyte infiltration.
Main Results:
- Dual 5-LO/CO inhibitors (phenidone, SKF 86002) and corticosteroids (prednisolone) significantly inhibited AA-induced MPO elevations in a dose-dependent manner.
- Selective cyclooxygenase inhibitors (indomethacin, ibuprofen, naproxen), anti-histamine/serotonin agents, and a gold compound showed minimal to moderate effects on MPO levels.
Conclusions:
- AA-induced hindpaw inflammation serves as a valuable in vivo model for assessing the pharmacological effects of 5-LO/CO inhibitors on PMN leukocyte infiltration.
- Dual inhibition of 5-LO and CO pathways appears more effective in reducing neutrophil infiltration during AA-induced inflammation compared to selective CO inhibition or other agents.