title: Stimulus- and cumulative dose-dependent inhibition of O2- production by polymorphonuclear leukocytes of patients receiving corticosteroids.
abstract: Since early in vivo studies in man have remained controversial as to the suppressive effects of glucocorticosteroids on the function of polymorphonuclear leukocytes (PMN), we tried to clarify those effects. The study population involved 19 inpatients on daily and prolonged corticosteroid therapy. Superoxide (O2-) production and chemotaxis were determined as a function of peripheral blood PMN, using various stimuli: concanavalin A (ConA) + cytochalasin D (CD), N-formyl-methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA), and the chemoattractants FMLP and zymosan activated serum (ZAS). In addition, the relationship between PMN function and corticosteroid dose was also evaluated. There was significant inhibition of PMN O2- production in the patients receiving corticosteroids depending on the stimulus (FMLP or PMA, 51% or 56% of controls; ConA + CD, not inhibited) but no significant inhibition of PMN chemotactic activity. Stimulation with FMLP showed an inverse relationship between O2- production and cumulative prednisolone dose (r = -0.41) in serial determination of O2- production in patients with a negative C-reactive protein (CRP) test. In the serial study of each patient with negative CRP we confirmed the suppression. These results suggest that O2- production by PMN could be inhibited, depending on the cumulative dose of corticosteroids in steroid-treated patients. This may be one possible mechanism of impaired host defences caused by corticosteroid therapy in man.
authors.affiliation: First Department of Internal Medicine, Kumamoto University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fukushima
authors.forename: M
authors.initials: M
authors.lastname: Ando
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Suga
authors.forename: S
authors.initials: S
authors.lastname: Araki
mesh_terms: D000328:Adult; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007107:Immune System / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects*; D013481:Superoxides / Q000097:blood / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
chemical_list: D003208:Concanavalin A; D013481:Superoxides; D015638:Cytochalasin D; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D011239:Prednisolone; D013755:Tetradecanoylphorbol Acetate