Da. Hart et al., EXOGENOUS RH-UROKINASE MODIFIES INFLAMMATION AND PSEUDOMONAS-AERUGINOSA INFECTION IN A RAT CHRONIC PULMONARY INFECTION MODEL, Canadian journal of microbiology, 39(12), 1993, pp. 1127-1134
The effect of recombinant human urokinase (rh-UK) in a rat model of ch
ronic Pseudomonas aeruginosa pulmonary infection was studied. Efficacy
was assessed by lung histology and quantitative bacteriology. Male Sp
rague-Dawley rats received 1 x 10(4) or 1 x 10(5) P. aeruginosa encaps
ulated in agar beads via the intratracheal route on day 1. Intratrache
al administration of up to 12 500 units of rh-UK on day 21 led to a do
se-dependent disappearance of viable organisms from the lungs by day 2
4 in rats receiving 10(4) organisms. In slightly longer term infection
s (30 days), rh-UK was still effective in facilitating the disappearan
ce of the organisms from the lungs of most of the treated animals. rh-
UK was effective in eliminating organisms when animals were infected w
ith 10(4), but not 10(5) bacteria. In vitro analysis revealed that rh-
UK was not directly toxic for the organisms. Histologically, lungs fro
m short-term infected control animals exhibited acute inflammation, in
flammatory cell infiltrates, and fibrin deposition. Histology of lungs
from UK-treated, short-term infected rats revealed decreased airway i
nflammation and cellular infiltration compared with infected controls.
Lungs from infected animals treated with 12 500 units of rh-UK were h
istologically indistinguishable from the lungs of uninfected control a
nimals, except for the foreign body reaction. These results indicate t
hat exogenous rh-UK may be efficacious in the treatment of pulmonary i
nflammation accompanying exposure to Gramnegative bacteria such as P.
aeruginosa.