Rats given an intravenous injection of Sephadex particles (0.5 mg of G200 in 1 ml of saline) on days 0, 2 and 5 had a blood eosinophilia which was maximal on day 7. On day 7, broncho‐alveolar lavage (BAL) fluids taken from the rats contained an increased number of eosinophils and fewer mononuclear cells but there was no change in the small number of neutrophils. In addition the rats were hyper‐sensitive to the increase in resistance to artificial respiration produced by 5‐hydroxytryptamine (5‐HT), given intravenously, with a shift to the left of the log dose‐response curve. Lung parenchymal strips, taken from the rats on days 6, 7 and 8, were hyper‐reactive to 5‐HT with an increase in slope of the log dose‐response curve. Compounds with a wide variety of activities were evaluated for their effects on the blood eosinophilia on day 7 when given before each injection of Sephadex. The eosinophilia was reduced by glucocorticosteroids, β‐adrenoceptor agonists, aminophylline, dapsone and phenidone. Dexamethasone, isoprenaline, dapsone and phenidone at doses that reduced the blood eosinophilia also reduced the changes in number of leucocytes in the BAL fluids and the hyper‐responsiveness to 5‐HT in vivo and in vitro, except that the effects of dapsone on the hyper‐sensitivity to 5‐HT in vivo did not reach significance. Aminophylline was the least effective of the drugs at reducing the blood eosinophilia and its effects on the other changes did not reach significance. Sodium cromoglycate reduced the BAL eosinophilia but had no effect on the other changes produced by Sephadex. The correlation coefficients between blood eosinophil numbers and reactivity to 5‐HT in vitro and sensitivity in vivo were r = 0.76, (n = 88; P > 0.001) and r = 0.53, (n = 61; P > 0.001) respectively. Doses of dexamethasone, isoprenaline, dapsone and phenidone that reduced the blood eosinophilia when given before each injection of Sephadex were inactive when given up to 8 h after the Sephadex. These data show an association between blood eosinophilia and hyper‐responsiveness of the lung. The blood eosinophilia in the rats was triggered within the first few hours of injecting the Sephadex and drugs have been identified which inhibit this trigger.

The injection of antigen into the peritoneal cavity of actively sensitised mice produced an increase in the number of neutrophils in peritoneal washings collected 4 h later but after 1 day the numbers had returned to control levels. The increase in numbers of mononuclear cells and eosinophils in the peritoneal washings peaked at 2 days and persisted for at least 5 days. Dosing the mice with phenidone, a dual inhibitor of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, potentiated the neutrophil infiltration at 4 h but had no significant effect upon the subsequent mononuclear cell and eosinophil infiltration. In contrast, treatment with the corticosteroid, dexamethasone, reduced the infiltration by all three types of cells, providing further evidence that the corticosteroids can inhibit immune-induced cellular infiltrations by mechanisms other than the inhibition of arachidonic acid metabolism. Isoprenaline, given to the mice before antigen challenge, had no effect on the subsequent neutrophil infiltration, but repeated doses did inhibit the mononuclear cell and eosinophil infiltration measured 4 days later. Aminophylline, disodium cromoglycate and cyproheptadine had no effect upon the cellular changes.

In rats, Sephadex treatment on days 0, 2 and either 4 or 5 resulted in a blood and lung eosinophilia, an increase in lung cell fragility, an increase in the functional activity of peritoneal eosinophils in vitro and a sustained increased responsiveness of lung parenchymal strips to KCl, 5-hydroxytryptamine (5-HT) and carbachol that was not associated with oedema or gross fibrosis. The corticosteroid dexamethasone, when given before each injection of Sephadex, reduced all these effects of Sephadex. When given 30 min after the last injection of Sephadex, dexamethasone had no effect on the number of blood and lung eosinophils but it did reduce the functional activity of peritoneal eosinophils, the increased lung cell fragility and the hyperresponsiveness to 5-HT. Repeated administration of dexamethasone to rats with an established hyperresponsiveness that was no longer associated with cellular inflammation had minimal effects on this hyperresponsiveness.

Changes occurring in the blood and the peritoneal cavity following the intraperitoneal injection of platelet-activating factor (PAF-acether) into rats were compared with those when antigen was injected intraperitoneally into actively sensitised rats. A blood eosinophilia had been produced in the rats by an intravenous injection of Sephadex G200 6 days before either challenge. 5 min after PAF-acether, the total number of cells in the peritoneal washings had decreased and the concentration of extravasated dye-labelled plasma protein had increased with no change in histamine levels. On the other hand, antigen at this time produced nor only a decrease in cells and an increase in dye but also an increase in histamine concentration. Only antigen produced a cellular infiltration into the peritoneal cavity with an increase in numbers of neutrophils in the peritoneal washings at 4 h and of mononuclear cells and eosinophils at 24 h. In the blood at 4 h after either challenge, there was a neutrophilia and an eosinopenia. When PAF-acether and antigen were injected together into actively sensitised rats, leucocyte counts in the peritoneal washings increased by a similar amount, both at 4 and 24 h, as those in rats given antigen alone.