Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease.
Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS)
Millar
A B
AB
Department of Medicine, University College and Middlesex School of Medicine, United Kingdom.
Miller
R F
RF
Foley
N M
NM
Meager
A
A
Semple
S J
SJ
Rook
G A
GA
D002478:Cells, Cultured; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008171:Lung Diseases / Q000209:etiology / Q000503:physiopathology*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha