The effects of anti-inflammatory and antiallergic drugs on the release of IL-1 beta and TNF-alpha in the human whole blood assay.
Heparinized human whole blood was evaluated as a model to study the effects of various classes of anti-inflammatory drugs on IL-1 beta and TNF-alpha release from leukocytes. Human whole blood was stimulated with zymosan (1.5 mg/ml) or LPS (5 micrograms/ml) to induce significant cytokine release. As previously reported, the 5-lipoxygenase/cyclooxygenase (5-LO/CO) inhibitor, SKF86002 (30 microM), significantly inhibited both IL-1 beta and TNF-alpha release using either stimulus. In contrast, the cyclooxygenase (CO) inhibitors (naproxen and ibuprofen) and the lipoxygenase (5-LO) inhibitors (zileuton, L-663536 and BWA4C) did not effect IL-1 beta or TNF-alpha release/biosynthesis. Isoproterenol (beta-agonist), rolipram (a PDE-IV inhibitor), and IBMX (a nonselective PDE inhibitor), significantly inhibited TNF-alpha but not IL-1 beta in the LPS model while having no effect in the zymosan model. This human whole blood assay is a unique and rapid method which can be used to identify novel inhibitors of IL-1 beta and TNF-alpha release/biosynthesis.
Hartman
D A
DA
Wyeth-Ayerst Research, Princeton, NJ 08543-8000.
Ochalski
S J
SJ
Carlson
R P
RP
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D007375:Interleukin-1 / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D007545:Isoproterenol