Differential in vitro regulation by glucocorticoids of monocyte-derived cytokine generation in glucocorticoid-resistant bronchial asthma.
We previously described a 3 kD neutrophil priming activity (NPA) derived from peripheral blood monocytes that is suppressed by glucocorticoid treatment of monocytes derived from individuals with corticosteroid-sensitive (CS) but not corticosteroid-resistant (CR) asthma. We compared the effects of glucocorticoids on the in vitro generation of other cytokines by monocytes of CS and CR asthmatic individuals. A total of 11 CS and 8 CR asthmatic subjects were studied. Monocytes were cultured overnight in the presence or absence of 5 micrograms/ml of lipopolysaccharide (LPS) with or without hydrocortisone (HC) or dexamethasone. TNF-alpha, IL-1 beta, and GM-CSF were measured by ELISA, mRNA for these cytokines were detected by northern analysis, and NPA was identified by its capacity to enhance ionophore-induced LTB4 generation from neutrophils. In the absence of LPS there was no significant difference in the generation of cytokines between monocytes derived from CS and CR individuals. Treatment of monocytes by 10(-6) M HC suppressed NPA generation from CS (72%, p = 0.002) but not CR subjects (10%, p = 0.47). In contrast there was no effect of glucocorticoids on the generation of other cytokines from monocytes of either CS or CR subjects. In the absence of LPS, mRNA for IL-1 beta and GM-CSF were not detected by northern analysis, and glucocorticoids had no significant effects on mRNA for TNF-alpha in either group. LPS at 5 micrograms/ml enhanced cytokine but not NPA generation and markedly increased cytokine mRNA in monocytes of both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Lane
S J
SJ
Department of Allergy and Allied Respiratory Disorders, United Medical School, Guy's Hospital, London, United Kingdom.
Wilkinson
J R
JR
Cochrane
G M
GM
Lee
T H
TH
Arm
J P
JP
D000328:Adult; D001249:Asthma / Q000276:immunology*; D015152:Blotting, Northern / Q000379:methods; D002478:Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology; D004351:Drug Resistance / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects
D016207:Cytokines; D005938:Glucocorticoids; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor