In order to develop a better management strategy for radiation-induced pulmonary injury,
we compared the protective effect of pretreatment and aftertreatment with different
doses of ulinastatin. Two hundred and forty female Sprague-Dawley rats were randomized
into five groups. Group R received radiation only, groups P1 and P2 were pretreated
with different doses of i.v. ulinastatin for 3 days pre- and 4 days post-irradiation,
and groups A1 and A2 were treated for 7 days post-irradiation only. Rats were sacrificed
at 2 h, and at 4, 8, 16, and 24 weeks post-irradiation. The expressions of TGF-beta1,
TNF-alpha, IL-6, hydroxyproline and laminin were determined. No adverse toxicological
effects of ulinastatin pretreatment were observed. Mortality and ratio of fibrotic
area was lowest in group P1(5/45; 30.6+/-3.11%, P<0.05 vs. A2). Expressions of TGF-beta1
and IL-6 in group P1 were significantly lowest at 4 weeks (3.01+/-0.35, 549+/-58,
32.3+/-3.27, P<0.01), and expressions of hydroxyproline and laminin were also lowest
at 24 weeks (741+/-68 and 82.6+/-6.91, P<0.01) in comparison with other groups. Significant
differences were observed in expression of TGF-beta1 and TNF-alpha in lung between
group P1 and group A1 at 4 weeks (263+/-11% vs. and 187+/-9%, 189+/-8% vs. 154+/-9%,
P<0.01, P<0.05 respectively). Pretreatment with high dose ulinastatin resulted in
a milder inflammatory response and suppressed pulmonary fibrosis, which may serve
as a favorable management strategy.