Local inflammatory responses following bronchial endotoxin instillation in humans.
To study local lung inflammation, 34 subjects had endotoxin (1-4 ng/kg) instilled into a lung segment and saline instilled into a contralateral segment followed by bronchoalveolar lavage (BAL) at 2 h, 6 h, 24 h, or 48 h. Endotoxin instillation resulted in a focal inflammatory response with a distinct time course. An early phase (2 h to 6 h) revealed an increase in neutrophils (p = 0.0001) with elevated cytokines (tumor necrosis factor [TNF]-alpha, TNF receptors [TNFR], interleukin [IL]-1beta, IL-1 receptor antagonist, IL-6, granulocyte-colony-stimulating factor [G-CSF], all p < or = 0.002, but no change in IL-10) and chemokines (IL-8, epithelial neutrophil activating protein-78, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, all p < or = 0.001, but no change in growth-regulated peptide-alpha). A later phase (24 h to 48 h) showed increased neutrophils, macrophages, monocytes, and lymphocytes (all p < or = 0.02), and a return to basal levels of most mediators. Elevated levels of inflammatory markers (TNFR(1), TNFR(2), L-selectin, lactoferrin, and myeloperoxidase) persisted in the BAL at 48 h (p < or = 0.001). Increased permeability to albumin occurred throughout both phases (p = 0.001). Blood C-reactive protein, serum amyloid A, IL-6, IL-1ra, G-CSF, but not TNF-alpha increased by 8 h (all p < or = 0.008). The local pulmonary inflammatory response to endotoxin has a unique qualitative and temporal profile of inflammation compared with previous reports of intravenous endotoxin challenges. This model provides a means to investigate factors that initiate, amplify, and resolve local lung inflammation.
O'Grady
N P
NP
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Preas
H L
HL
Pugin
J
J
Fiuza
C
C
Tropea
M
M
Reda
D
D
Banks
S M
SM
Suffredini
A F
AF
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001999:Bronchoscopy; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils; D010865:Pilot Projects
D018925:Chemokines; D016207:Cytokines; D004731:Endotoxins; D018836:Inflammation Mediators