Synergistic and additive killing by antimicrobial factors found in human airway surface liquid

Airway surface liquid contains multiple factors thought to provide a first line of defense against bacteria deposited in the airways. Although the ant imicrobial action of individual factors has been studied, less is known abo ut how they work in combination. We examined the combined action of six ant imicrobial peptides found in airway surface liquid. The paired combinations of lysozyme-lactoferrin, lysozyme-secretory leukocyte protease inhibitor ( SLPI), and lactoferrin-SLPI were synergistic. The triple combination of lys ozyme, lactoferrin, and SLPI showed even greater synergy. Other combination s involving the human beta -defensins, LL-37, and tobramycin (often adminis tered to cystic fibrosis patients by inhalation) were additive. Because the airway surface liquid salt concentration may be elevated in cystic fibrosi s patients, we examined the effect of salt on the synergistic combinations. As the ionic strength increased, synergistic interactions were lost. Our d ata suggest that the antibacterial potency of airway surface liquid may be significantly increased by synergistic and additive interactions between an timicrobial factors. These results also suggest that increased salt concent rations that may exist in cystic fibrosis could inhibit airway defenses by diminishing these synergistic interactions.