The complement regulators C1 inhibitor and soluble complement receptor 1 attenuate acute lung injury in rabbits

Because activation of the complement system plays a major role in the patho genesis of acute lung injury, the availability of new specific complement i nhibitors represents a promising therapeutic approach. In the present study we investigated pulmonary edema formation and pulmonary artery pressure (P AP) in acute complement-induced lung injury for possible therapeutic impact of the complement regulators C1 inhibitor and soluble complement receptor I. Eighteen isolated and ventilated rabbit lungs were perfused with pooled normal human serum (NHS, final concentration 35%) in Krebs-Henseleit buffer in a recirculating system. Lung weight gain and PAP were continuously reco rded. Complement activation was blocked by the addition of C1 inhibitor (1. 0 U/mL, n = 6) or sCR 1 (2.0 mu g/mL, n = 6). Lungs that received NHS witho ut inhibitors served as controls (n = 6). This study was performed accordin g to the Helsinki Declaration and approved by the local government. Applica tion of NHS resulted in an increase of PAP within 20 min from 8 +/- 2 to 42 +/- 6 mmHg, which was significantly (P < 0.05) decreased by C1-Inh (25 rt 5 mmHg) and sCR1 (20 +/- 3 mmHg). Moreover, pulmonary edema formation after NHS, as assessed by overall weight gain, was reduced by both C1-Inh and sC R1, compared with controls. These findings were paralleled with significant ly decreased thromboxane release rates and reduced tissue deposition of C3c and C5b-9. C1 inhibitor and sCR1 attenuate the complement-induced pulmonar y capillary leakage and PAP increase, indicating the protective effect of c omplement inhibition in isolated perfused rabbit lungs.