and degranulation of neutrophils (polymorphonuclear leukocytes
[PMNs]) may contribute to severe lung injury in patients with ARDS.
Interleukin-8 (IL-8), a potent neutrophil attractant and activator, has
been implicated in the PMN recruitment. Due to increased epithelial and
endothelial permeability, which occurs in association with ARDS,
higher-molecular-weight proteins, such as IgG and IgM, enter airspaces.
Our previous studies show that a significant portion of IL-8 in lung
fluids from patients with ARDS is associated with anti-IL-8
autoantibodies (anti-IL-8:IL-8 complexes). In addition, our earlier
findings suggest that these autoantibodies to IL-8 may be important in
controlling IL-8 function by neutralizing its biological activity
and/or facilitating clearance of IL-8 by the reticuloendothelial
system. To further define the function of these autoantibodies in ARDS
patients, we measured concentrations of free and complexed IL-8 in BAL
fluids from 19 patients at risk for ARDS and 40 patients with
well-defined ARDS (1, 3, 7, 14, and 21 days after the onset of ARDS).
Patients at risk for ARDS had less anti-IL-8:IL-8 complexes than
patients with ARDS (day 1). In ARDS, the highest concentration occurred
in patients who died, and the concentrations did not decline with time.
In contrast, in survivors, the concentrations were significantly lower
and declined with time. The increased amount of anti-IL-8:IL-8
complexes was associated with the development of ARDS in patients at
risk and death in patients with ARDS. Both free IL-8 and anti-IL-8:IL-8
complexes correlated with concentrations of PMNs (p < 0.05;
r2 = 0.60 and 0.30, respectively) in patients at risk for
ARDS. In ARDS patients, anti-IL-8:IL-8 complexes correlated with PMNs
on day 3, whereas free IL-8 correlated with PMNs on days 3, 7, and 14.