The relative efficacy of mucosal (intratracheal) and systemic (intraperitoneal) delivery of
interleukin (IL)-12 was evaluated in a mouse model of allergic lung
eosinophilia.
Mucosal administration of
IL-12 achieved 100- to 600-fold higher bronchoalveolar lavage (BAL) levels of
IL-12, but 2- to 10-fold lower serum levels compared to systemic administration. Whereas both mucosal and systemic
IL-12 inhibited BAL eosinophil recruitment at high doses (100-1000 ng), only mucosal
IL-12 was effective at low doses (1-10 ng). Mucosal, but not systemic, administration of 1000 ng of
IL-12 increased
interferon (IFN)-gamma expression in BAL cells. In a model of ongoing eosinophilic
inflammation, when mucosal or systemic
IL-12 doses were initiated prior to peak
eosinophilia, further eosinophil recruitment was inhibited. However, when
IL-12 treatment was initiated after peak eosinophil recruitment occurred, recovery from eosinophilic
inflammation was not facilitated. Our findings are the first to demonstrate that locally administered
IL-12 inhibits eosinophil recruitment at 100-fold lower doses than systemic
IL-12. The most likely mechanism of this enhanced inhibitory activity is a sustained increase in lung levels of
IL-12 that augments IFN-gamma production from BAL cells. We suggest that future studies should evaluate the efficacy of low doses of nebulized
IL-12 in inhibiting eosinophilic
lung inflammation in
asthma.