ANTI-IL-8 AUTOANTIBODIES IN ALVEOLAR FLUID FROM PATIENTS WITH THE ADULT-RESPIRATORY-DISTRESS-SYNDROME

IL-8 is a potent neutrophil attractant and activator, IL-8 has been re ported to be involved in the pathogenesis of several diseases, includi ng rheumatoid arthritis, sepsis, psoriasis, and the adult respiratory distress syndrome (ARDS), Our previous studies demonstrated that high concentrations of IL-8 were present in alveolar fluids from patients w ith ARDS and were associated with increased mortality, In this study w e report that a major portion of IL-8 in bronchoalveolar fluids from p atients with ARDS is associated with anti-IL-8 autoantibody (anti-IL-8 :IL-8 complexes), Free autoantibodies that recognize IL-8 were also de tected in these fluids, Next, we examined the properties of anti-IL-8 autoantibodies present in lung fluids from ARDS patients and compared them with autoantibodies from normal plasma and arthritic synovial flu ids, The anti-IL-8 autoantibody was poly-clonal, and IgG3 and lgG4 wer e the primary IgG subclasses, Anti-IL-8:IL-8 complexes consisted of on e Ige and one IL-8 molecule, In addition, anti-IL-8 autoantibody bound IL-8 with a high affinity (similar to 10(-12)M) and inhibited IL-8 in teraction with its specific receptors on neutrophils. The results sugg est that anti-IL-8 autoantibodies may regulate IL-8 activity.