Effects of Corticosteroids on Eosinophil Chemotaxis and Adherence

Abstract

A B S T R A C T Therapeutic doses of corticosteroids frequently induce eosinopenia; however, the mechanism(s) involved remain obscure. To investigate this question, we studied the effects of corticosteroids on eosinophil adherence and migration. Eosinophils from normal donors were prepared by dextran sedimentation and Hypaque gradient centrifugation to 45-96% purity. Adherence was measured by filtration of whole blood and isolated eosinophils through nylon wool columns. Before prednisone administration, adherence was 83.8+3.2% for eosinophils in heparinized blood and 82.1±3.2% for isolated eosinophils. 4 h after oral prednisone administration whole blood eosinophil adherence was reduced to 53.9+10.7%; at 24 and 48 h adherence was normal. In contrast, isolated eosinophils showed no decrease in adherence 4, 24, or 48 h after corticosteroid administration. Similarly, in vitro addition of hydrocortisone to isolated eosinophils at 0.01 and 2.0 mg/ml did not reduce adherence. Eosinophil migration was tested in modified Boyden chambers by "lower-surface" and "leading-front" methods, using zymosan-activated serum and buffered saline to assess chemotactic and random migration, respectively. In vitro incubation of eosinophils with hydrocortisone or methylprednisolone produced a dose-dependent inhibition ofchemotaxis. Using lowersurface methods the minimal concentration effecting substantial inhibition was 0.01 mg/ml for both drugs. At 2.0 mglml hydrocortisone and methylprednisolone inhibited eosinophil chemotaxis 82.6±4.4% and 85.0±3.5%, respectively. Using leadiig-front chemotaxis techniques significant inhibition was detected at 0.001 mg/ml hydrocortisone. Eosinophils incubated and washed free of corticosteroids responded normally to chemoattractants, indicating that the inhibitory effect of these drugs was reversible. HydroAddress reprint requests to Dr. Altman. Received for publication 21 March 1979 and in revised form 18 September 1980. 28 cortisone at 2 mg/ml inhibited random eosinophil migration, although this effect was not apparent at lower concentrations. Corticosteroids did not act as chemotactic factor inactivators and were not toxic as measured by trypan blue exclusion. Eosinophils obtained from donors who had received 40 mg of prednisone orally for four days showed normal chemotactic responses, probably reflecting the fact that the cells were washed free of plasma before testing. In contrast, incubation of eosinophils in plasma from donors who had received a 300-mg bolus of hydrocortisone induced 46.1±4.5% more inhibition of chemotaxis than did incubation in normal plasma. These results indicate that: (a) eosinophil adherence is transiently reduced following in vivo corticosteroid administration, (b) eosinophil chemotaxis is inhibited by both in vitro and in vivo administration of corticosteroids, and (c) the chemotaxis inhibiting effect is nontoxic, cell-directed, dose-dependent and reversible. Inhibition of eosinophil adherence and chemotaxis may in part explain how corticosteroids produce eosinopenia a...

Allergen-induced late-phase airways obstruction in the pig: mediator release and eosinophil recruitment

“…Eosinophils are highly sensitive to glucocorticoids: eosinophil chemotaxis, migration and adherence to endothelium are blocked, primarily because glucocorticoids decrease the expression of stimulating cytokines [13]. In this study, no blood eosinophils were detected at 8 h in pigs with high cortisol levels.…”

“…Cys-LTs have also been shown to recruit eosinophils when given to asthmatics [11], and to induce latephase bronchoconstrictor reactions in sheep [12]. Since the activity of eosinophils is reduced by glucocorticoids [13], it was of interest to evaluate the effects of endogenous cortisol on eosinophil recruitment as well as mediator release. In the present study, this was done by pretreatment of the animals with metyrapone, a cortisol-synthesis inhibitor [14].…”

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part II)

“…Corticosteroids are likely to have a multifactorial therapeutic effect, resulting from the suppression of the regulatory mechanisms of the immune response, migratory action, as well as the distal effector functions of eosinophils. For instance, corticosteroids reduce the number of sputum [448], and peripheral blood eosinophils [152,410,[449][450][451], presumably through a decreased release from the bone marrow [452], a reduction in eosinophil survival [453,454], and inhibition of eosinophil tissue infiltration probably by inhibiting both eosinophil chemotaxis [455,456] and adherence to endothelium [47, [457][458][459]. Corticosteroids also diminish antibody-dependent eosinophil cytotoxicity [460].…”

The effect of 2 weeks treatment with cetirizine on bronchial reactivity to methacholine in asthma.

“…One would expect drugs with inhibitory effects on eosinophils both to protect against increases in BHR following allergen challenge in the laboratory, and to reduce baseline BHR in asthmatics in the community. Of the available antiasthma drugs, corticosteroids are of proven clinical efficacy, and have well documented effects on eosinophils, both in reducing circulating numbers and inhibiting chemotaxis (Altman et al, 1981). When administered prior to allergen challenge in the laboratory, corticosteroids inhibit the late response, and the associated increase in BHR (Cockcroft & Murdock, 1987).…”