THE EFFECTS OF ANTIINFLAMMATORY 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-1beta and TNF-alpha release from leukocytes. Human whole blood was stimulated with zymosan (1.5 mg/ml) or LPS (5 mug/ml) to induce significant cytokine release. As previously reported, the 5-lipoxygenase/cyclooxygenase (5-LO/CO) inhibitor, SKF86002 (30 muM), significantly inhibited both IL-1beta 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-1beta 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-1beta 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-1beta and TNF-alpha release/biosynthesis.