In vitro testing for lung toxicity: a method for distinguishing between immune- and non-immune-mediated reactions to...

Knowledge of whether a given toxicant produces its effects through direct or immune mechanisms should prove useful in predicting variability of the toxic response. This paper presents preliminary findings from biochemical studies conducted in perfused and ventilated guinea-pig lung to examine the release of arachidonic acid metabolites and vasoactive intestinal polypeptide associated with various types of lung injury. Anaphylaxis provoked with ovalbumin challenge in sensitized lungs was associated with increases in products of both cyclo-oxygenase (thromboxane A(2) prostaglandin E(2)) and lipoxygenase (leukotrienes B(4) and C(4)) metabolism. Xenobiotics that cause direct bronchial irritation (formaldehyde, acid water) produced increases only in cyclo-oxygenase activity. Anaphylactic bronchospasm was also associated with increased release of vasoactive intestinal polypeptide. These findings suggest that in vitro immune-mediated bronchospastic reactions to xenobiotics might be distinguished on the basis of the arachidonic acid metabolites and/or VIP they release.