42.06 Inhaled IL10 Decreases the Development of Pulmonary Hypertension in Slit3 Knockout Mice with CDH

Posted on January 25, 2017

M. Shah1, M. R. Phillips1, S. Balaji2, S. G. Keswani2, S. E. McLean1  1University Of North Carolina At Chapel Hill,Chapel Hill, NC, USA 2Baylor College Of Medicine,Houston, TX, USA

Introduction:
Congenital diaphragmatic hernia (CDH) is associated with pulmonary arterial hypertension (PAH). There is an increase in inflammatory cell invasion in pulmonary arteries in CDH. Slit3 knockout (KO) mice with CDH develop PAH over time, with no evidence of PAH at 2 weeks of age, but presence of PAH at 4 weeks of age. We hypothesize that treatment of 2 week old Slit3 KO mice with CDH that have yet to develop PAH, with inhaled IL10, an anti-inflammatory cytokine, will decrease the development of PAH in CDH.

Methods:
Slit3 wild-type (WT) (n=5) and KO (n=5) mice were analyzed at 2 weeks of age. Mice were treated with IL10 mixed with hydrogel, administered intranasally, at day 0 and day 7. Echocardiography was performed pre-IL10 (day 0) at 2 weeks of age and post-IL10 treatment (day 14) at 4 weeks of age. Right ventricular (RV) systolic pressures were obtained by direct cardiac puncture post-IL10 treatment (day 14) at 4 weeks of age. 

Results:
Pre-IL10 treatment, the pulmonary artery (PA) flow of KO mice was similar to WT, with PA velocity time indices (VTI), 20.95 mm vs. 21.80 mm (p=0.49), PA peak velocities, 546.59 mm/s vs. 547.86 mm/s (p=0.97), and pulmonary acceleration times (PAT), 11.1 ms vs. 12.22 ms (p=0.12), respectively. Post-IL10 treatment at 4 weeks of age, there was still similar PA flow in KO and WT mice, with PA VTI, 26.19 mm vs. 24.05mm (p=0.34), and PAT, 11.72 ms vs. 11.28 ms (p=0.67). PA peak velocity was altered in KO vs WT mice, however, 809.7 mm/s vs. 667.48 mm/s, respectively (p<0.05). Post-IL10 treatment, RV systolic pressure was similar in KO (n=3) and WT (n=4) mice, 19.38 mmHg vs. 18.22 mmHg, respectively (p=0.54).

Conclusion:
2 week old Slit3 KO mice with CDH that have yet to develop PAH show decreased development of PAH and maintenance of RV systolic pressures at 4 weeks of age after treatment with inhaled IL10. IL10 may play an anti-inflammatory role that ameliorates PAH in CDH.