Tumor necrosis factor (TNF) was measured antigenically and functionally in serum and bronchoalveolar lavage fluid (BAL) of patients with ARDS and those at high risk for ARDS. Of 22 patients with ARDS, 14 had sepsis or serious infection as the major clinical predisposition, and 10 of 20 high-risk patients had sepsis or serious infection. Mean levels of TNF in serum of patients with ARDS and high risk showed a trend toward elevation but were not significantly higher than mean serum levels in normal subjects. Mean levels of TNF in BAL of ARDS patients (242 +/- 126 pg/ml) were significantly higher than in normal subjects (9 +/- 5 pg/ml), p less than 0.05. Antigenic levels of TNF were undetectable in approximately half the patients with ARDS or the high-risk state. Levels of TNF in BAL appeared to be highest in the first day of ARDS. There appeared to be no relationship between levels of TNF in serum or BAL and subsequent mortality. However, serum levels of TNF were significantly higher in septic patients than in nonseptic patients, whereas this difference was not apparent in BAL. These results show that functional and antigenic elevations of TNF are present in BAL and perhaps in serum of patients with ARDS or with the high-risk state.
Serum levels of the acute-phase reactant, C-reactive protein (CRP), increase dramatically during acute inflammatory episodes. CRP inhibits migration of neutrophils toward the chemoattractant, f-Met-Leu-Phe (fMLP) and therefore acts as an anti-inflammatory agent. Since tyrosine kinases are involved in neutrophil migration and CRP has been shown to decrease phosphorylation of some neutrophil proteins, we hypothesized that CRP inhibits neutrophil chemotaxis via inhibition of MAP kinase activity. The importance of p38 MAP kinase in neutrophil movement was determined by use of the specific p38 MAP kinase inhibitor, SB203580. CRP and SB203580 both blocked random and fMLP-directed neutrophil movement in a concentration-dependent manner. Additionally, extracellular signal-regulated MAP kinase (ERK) was not involved in fMLP-induced neutrophil movement as determined by use of the MEKspecific inhibitor, PD98059. Blockade of ERK with PD98059 did not inhibit chemotaxis nor did it alter the ability of CRP or SB203580 to inhibit fMLP-induced chemotaxis. More importantly, CRP inhibited fMLP-induced p38 MAP kinase activity in a concentration-dependent manner as measured by an in vitro kinase assay. Impressively, CRP-mediated inhibition of p38 MAP kinase activity correlated with CRP-mediated inhibition of fMLP-induced chemotaxis (r ؍ ؊0.7144). These data show that signal transduction through p38 MAP kinase is necessary for neutrophil chemotaxis and that CRP intercedes through this pathway in inhibiting neutrophil movement.
These results demonstrate that inflammation does occur during tracheal intubation, even when markers suggest minimal tracheal damage. The dramatic elevation in polymorphonuclear cells, along with the increase in interleukin 6, suggests an inflammatory response to the endotracheal tube itself or to some aspect of the intubation process. A more complete understanding of the response of the tracheal tissues is important in improving the treatment of intubated patients.
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