Background Both CC10, a clara cell secreted protein, and Muc1, a membrane-bound lung epithelia mucin, are present extracellularly, are anti-inflammatory, and deficient in the immature lung. We have shown previously that surfactant treatment (SFT), followed by recombinant human CC10 (rhCC10) treatment, reduces inflammation (J Appl Physiol 2005;99:2204–11). However, it is unknown if there is a corresponding response to rhCC10 and SFT on the intrinsic pro/anti-inflammatory milieu in the immature lung. Objective Assess the endogenous CC10 and Muc1 response to rhCC10 in the preterm lung. Methods 24 premature lambs (126 ± 3 SD days) were anesthetized, instrumented, delivered, paralyzed, and ventilated. Lambs were randomized to 4 groups (n=6/group) following baseline measurements: untreated (UNT), SFT (Survanta® 100mg/kg; 4ml/kg), or SFT followed by intratracheal rhCC10 (0.5 or 1.5 mg/kg; 2 ml/kg). After 4 hrs, lung tissue was harvested for Muc1 and IL-8 ELISAs, CC10 western blot, and qPCR analysis. Results Treatment Groups UNT SFT SFT + 0.5 mg/kg rhCC10 SFT + 1.5 mg/kg rhCC10 Relative Endogenous CC10 mRNA Exp (x 10−3) 6.93 ± 1.66 6.40 ± 3.60 8.29 ± 2.35 0.70 ± 0.41* Muc1 (Abs × 10−3) 4.6 ± 0.20 3.9 ± 0.57 4.1 ± 0.87 3.0 ± 0.53* IL-8 (ng/mg protein) 17.70 ± 2.11 21.58 ± 1.75 20.55 ± 1.71 12.85 ± 3.32* Mean ± SEM (*p < 0.05 vs other groups) Conclusions These data demonstrate that both pro- and anti-inflammatory profiles in the immature lung are responsive to rhCC10 in a dose dependent manner. We speculate that the anti-inflammatory action of rhCC10 down regulates intrinsic anti-inflammatory pathways. Further work using lung epithelial cell culture to analyze downstream CC10 and Muc1 pathways and western analysis of CC10 are ongoing. Supp.: NIH 5T32HL091804; P20RR020173; RO1 HL-47125; Clarassance, Inc. (Claragen, Inc.); Ross Labs.