The kinetics of the appearance of cytokines and mediators of inflammation was determined in normal subjects and in selected patients with abnormal host defense. For this study a model of inflammation in the skin was employed using a blister device. In normal subjects C5a, LTB4, and gamma-interferon appeared within 3 h of raising blisters, Il-8 and Il-6 appeared from 8 through 24 h and Ill-B, GM-CSF and TNF-alpha appeared from 12 to 24 h. In vitro studies indicated that exudate neutrophils are capable of TNF-alpha. production. Studies in patients with chronic granulomatous disease revealed normal mediator accumulation in these patients. In contrast, patients with the hyperimmunoglobulin E-recurrent infection (HIE) syndrome had about ten-fold increased TNF-alpha accumulation in the blister fluid. The increased TNF-alpha was restricted to the local inflammatory response since in related studies, in which a preparation of the lipid A component of E. coli endotoxin was administered intravenously to normal volunteers and HIE subjects, normal increases in TNF-alpha, Il-8 and Il-6 in the circulation in HIE subjects was observed. Abnormal regulation of TNF-alpha at local inflammatory sites may have important implications in the pathogenesis of the post infectious complications seen in HIE such as bronchiectasis and bronchopleural fistula formation following pneumonia.
