BLOOD INFLAMMATORY RESPONSE TO INHALED ENDOTOXIN IN NORMAL SUBJECTS

Previously we have reported that in asthmatics an inhalation of 20 mu g lipopolysaccharide (LPS) produces a bronchial obstruction associated with an inflammatory blood response. The aim of the present study was to evaluate this response in normal subjects. Eight normal non-atopic subjects were challenged by inhalation of a solution containing 20 mu g LPS (from Escherichia coli 026:B6) a week after bronchial challenge with control solution. The lung function response was evaluated by th e changes in forced expiratory volume in one second (FEV(1)), in speci fic conductance and in airway resistance while the blood inflammatory response was evaluated by serial measures of total white blood cells ( WBC) and polymorphonuclear neutrophils (PMN) count, luminol enhanced-c hemiluminescence (luminol-CL, as a marker of the PMN degree of activat ion), C-reactive protein (CRP), haptoglobin, complement fraction C3, t umour necrosis factor-alpha (TNF-alpha) and adrenocorticotropic hormon e (ACTH). No response in lung function was observed for 6 h after the LPS inhalation. The count in WBC and PMN increased 300 (P < 0.01) and 360 (P < 0.01) min after the LPS challenge associated with an increase in the level of luminol-CL (P < 0.001). This rise in luminol-CL level was significant at 120 min (P < 0.05) before any change in the PMN co unt. After 24 and 48 h the acute-phase protein CRP raised significantl y (P < 0.01), the other proteins C3 and haptoglobin being unchanged. A slight increase in ACTH was observed 240 and 360 min (P < 0.05) after the LPS challenge while the TNF alpha detectable level was not modifi ed. In conclusion, in normal subjects, inhalation of a pro-inflammator y agent is able to induce a systemic inflammatory response in the abse nce of any effect on lung mechanics, while in asthmatics the same bron chial challenge has been reported to induce a similar blood inflammati on associated with a significant response in lung function.