Selective enhancement of GM-CSF, TNF-alpha, IL-1 beta and IL-8 production by monocytes and macrophages of asthmatic subjects.
Previous work has demonstrated an increase in the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by monocytes derived from asthmatic individuals. We have suggested that monocytes and macrophages enhance airways inflammation by augmented cytokine production. We tested this hypothesis by measuring the production of GM-CSF and macrophage-derived cytokines, namely interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8), from unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood monocytes and alveolar macrophages in 31 asthmatic and 11 normal, control subjects. The basal production of GM-CSF was four fold higher in the monocytes of asthmatic individuals, but there was no significant difference in the basal production of TNF-alpha, IL-1 beta and IL-8. After stimulation with LPS, asthmatic monocytes produced twofold more GM-CSF and fourfold more IL-1 beta than the monocytes from control subjects. Unstimulated macrophages from asthmatic subjects produced significantly less GM-CSF and TNF-alpha than macrophages from controls, and there was no difference in either IL-1 beta or IL-8 production. When stimulated by LPS, macrophages from asthmatic subjects produced twofold more GM-CSF, threefold more TNF-alpha and fourfold more IL-8. The levels of IL-8 produced by both monocytes and macrophages were at least 20 fold higher than those of the other cytokines measured. There is selectivity in the upregulation of cytokine production by monocytes and macrophages in asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
Hallsworth
M P
MP
Dept of Allergy and Allied Respiratory Disorders, UMDS, Guy's Hospital, London, UK.
Soh
C P
CP
Lane
S J
SJ
Arm
J P
JP
Lee
T H
TH
D000328:Adult; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor