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 intravenous injection of Sephadex particles (G200) into rats produced a specific increase in numbers of blood eosinophils peaking 7 days later. A second injection, given on day 14 when the numbers of blood eosinophils had fallen to control levels, produced a dose-dependent increase in numbers, greater than the first, and peaking 5 days later. At this time there was a dose-dependent increase in numbers of eosinophils, but not of other leucocytes, in broncho-alveolar lavage fluids and lung tissue, together with an increase in sensitivity of the rats to the respiratory effect produced by the intravenous injection of 5-hydroxytryptamine.

The injection of antigen into the peritoneal cavities of actively sensitised rats produced an immediate reaction characterised by an increase in concentrations in the peritoneal fluids, collected 5 min later, of extravasated dye labelled plasma proteins, histamine and slow reacting substance of anaphylaxis (SRS-A). Changes were also produced in the numbers of leucocytes in the blood and peritoneal cavity. 5 min after antigen challenge there was a reduction in the number of cells that could be washed from the peritoneal cavity. 4 h after antigen there was an increase in numbers of neutrophils both in the blood and peritoneal washings and these fell to the levels in control rats at 24 h. 24 h after antigen, and continuing for 72 h, there was an increase in numbers of eosinophils and mononuclear cells in the peritoneal washings. The rats were injected intravenously with sephadex particles to produce a blood eosinophilia at the time of antigen challenge, this increased the numbers of eosinophils migrating into the peritoneal cavity but had no effect on antibody levels, the numbers of other leucocytes or on the immediate reaction. An inhibitor of lipoxygenase and cyclo-oxygenase metabolism of arachidonic acid, phenidone, at 100 mg/kg p.o., inhibited SRS-A release to control levels, in the immediate reaction, but had no effect on the leucocyte changes. The glucocorticosteroid, dexamethasone, at doses of 0.1 and 1 mg/kg p.o., produced little inhibition of SRS-A release but significantly inhibited neutrophil, eosinophil and mononuclear cell infiltration into the peritoneal cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

The intravenous injection of Sephadex particles (G200) into rats produced a specific increase in numbers of blood eosinophils, peaking 7 days later. A second injection, given on day 14 when the numbers of blood eosinophils had fallen to control levels, produced a dose-dependent increase in numbers, greater than the first, and peaking 5 days later. At this time, there was a dose-dependent increase in numbers of eosinophils, but not of other leucocytes, in broncho-alveolar lavage fluids and lung tissue, together with an increase in sensitivity of the rats to the respiratory effects produced by the intravenous injection of 5-hydroxytryptamine.