Cultured alveolar macrophages from patients with idiopathic pulmonary fibrosis (IPF) show dysregulation of lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) inductions.
Regulation of the pulmonary host defence mechanism is crucial for protection of the lung without pathological consequences. This is exemplified in the normal lung by the induction of both the pro-inflammatory cytokine TNF-alpha, its receptors and the anti-inflammatory cytokine IL-10 by bacterial lipopolysaccharide (LPS). We have evaluated this mechanism in patients with idiopathic pulmonary fibrosis (IPF). Alveolar macrophages (AM) were obtained by bronchoalveolar lavage from 21 subjects with IPF and 12 healthy volunteers. Constitutive and LPS-stimulated AM production of TNF-alpha, TNF soluble receptors CD120a and CD120b, and IL-10 at the protein and mRNA level were measured by bioassay, ELISA and competitive PCR respectively. AM from IPF subjects were more susceptible to LPS induction of TNF-alpha protein (P = 0.03) and transcription of IL-10 mRNA (P = 0.01) and IL-10R1 (P = 0.01) expression in comparison to controls. In contrast, increased CD120b was present as protein and mRNA compared to controls (P = 0.02). AM from IPF subjects were at least as susceptible to down-regulation of LPS-induced TNF-alpha levels by exogenous IL-10 as normal controls (94% versus 63%). These data suggest that there is dysregulation of LPS-induced TNF-alpha and IL-10 in AM from IPF subjects. Further studies are required to elucidate these observations, which may, in turn, give additional insight into the pathogenesis of this disease.
Freeburn
Robin W
RW
Lung Research Group, University of Bristol Medical School Unit, Southmead Hospital, Westbury on Trym, Bristol, BS10 5NB, UK.
Armstrong
Lynne
L
Millar
Ann B
AB
D000328:Adult; D000368:Aged; D018893:Bronchoalveolar Lavage; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053701:Receptors, Interleukin-10; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000096:biosynthesis; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000096:biosynthesis; D048069:Tumor Necrosis Factors / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D048069:Tumor Necrosis Factors; D016753:Interleukin-10