Effects of corticosteroids on cytokine generation and expression of activation antigens by monocytes in bronchial asthma.
The capacity of corticosteroids to inhibit the secretion of cytokines and the expression of selective antigens on monocytes has been studied in corticosteroid-sensitive (CS) and corticosteroid-resistant (CR) asthmatic patients. Incubation of monocytes derived from CS subjects with hydrocortisone inhibited the production of the enhancing activity, whereas in CR subjects hydrocortisone at concentrations of up to 10(-4) M did not suppress the release of enhancing activity. There was a rank order of potency for corticosteroid action: hydrocortisone less than methylprednisolone less than dexamethasone. The major activity was characterized as a heat-sensitive peptide of 3,000 daltons. The expression of CR1, CR3 and class II on asthmatic peripheral-blood mononuclear cells was increased relative to normal control donors. Culturing monocytes for 24 h in the presence of 10(-4) M hydrocortisone inhibited the expression of CR1, CR3 and class II in CS subjects but not in CR individuals. These results suggest that monocytes of CR asthmatic patients can increase the inflammatory potential of neutrophils and that they are hyperactive, as indicated by increased cytokine production and enhanced expression of activation markers, despite the presence of corticosteroids.
Wilkinson
J R
JR
Department of Allergy and Allied Respiratory Disorders, Guy's Hospital, London, UK.
Lane
S J
SJ
Lee
T H
TH
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016177:Macrophage-1 Antigen / Q000032:analysis; D009000:Monocytes / Q000276:immunology*; D011951:Receptors, Complement / Q000032:analysis; D017463:Receptors, Complement 3b
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D006684:HLA-DR Antigens; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D017463:Receptors, Complement 3b