Recombinant secretory leukoprotease inhibitor (rSLPI), a recombinant form of a natural airway inhibitor of neutrophil elastase (NE), is a potential therapeutic agent for cystic fibrosis (CF), a condition characterized by airway derangement mediated in part by the large burden of NE on the CF respiratory epithelial surface. After in vitro studies that demonstrated that aerosolized rSLPI retains its form and function, rSLPI was administered via aerosol to normal individuals and individuals with CF to determine the pharmacokinetics of in vivo rSLPI augmentation of the anti-NE defenses of the respiratory epithelial surface. After rSLPI aerosolization to normal individuals (100 mg single dose or 100 mg twice daily for 1 wk) there was a marked increase in SLPI levels and anti-NE capacity in airway epithelial lining fluid (ELF) at 1 h, diminishing gradually over 4 to 12 h. Interestingly, the ELF SLPI levels and anti-NE capacity achieved 12 h after 1 wk of rSLPI aerosols were no different than those 12 h after a single dose of rSLPI, suggesting that rSLPI does not accumulate on the respiratory epithelial surface after aerosolization. The ability of rSLPI to suppress NE in vivo was evaluated by aerosolization of rSLPI to individuals with CF, first as an escalating dose to assess safety, and then at doses of 100 mg twice daily for 1 wk or 50 mg twice daily for 2 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

We demonstrate a differential expression of IL-2R+ and MCH II+ on CD45RO+ T helper cells that would suggest that there are three subsets of activated memory T helper cells in asthmatics. Two non-overlapping IL-2R+ or MHC II+ CD45RO+ T helper cells and a third subpopulation of activated cells that coexpress IL-2R and MHC II (double positives). This latter subpopulation is significantly higher in asthmatics (acute or stable) compared with both non-asthmatic groups, suggesting a specific T helper activation phenotype distinct to atopic asthmatics as compared with atopic non-asthmatics.