TLQP-21 modulate inflammation and fibrosis in a model of ards

Abstract

Issue Title: ESICM LIVES 2015

Pozzi et al. Intensive Care Medicine Experimental 2015, 3(Suppl 1):A562 http://www.icm-experimental.com/content/3/S1/A562

POSTER PRESENTATION Open Access

TLQP-21 modulate inflammation and fibrosis in a model of ards

F Pozzi1*, L Rizzi1, V Zambelli1, L Molteni1, M Cavagna1, P Verdie2, J-A Fehrentz2, J Martinez2, A Torsello1, G Bellani1 , A Pesenti1

From ESICM LIVES 2015Berlin, Germany. 3-7 October 2015

Introduction

TLQP-21 is a neuropeptide expressed in the brain that is involved in the control of energy homeostasis. In preliminary experiments we have observed that TLQP-21 can modulate macrophage function. In Acute Respiratory Distress Syndrome (ARDS) macrophage seems to play a critical role, contributing to lung remodeling.

Objectives

To explore the therapeutic role of a short analog of TLQP-21 (JMV5656) in an experimental model of ARDS.

Methods

C57/BL6 mice received an instillation of 0.1 M HCl, 2.5 ml/kg into the right bronchus. They were treated with TLQP-21 0.6 mg/kg ip or vehicle control, 2 days before and on the same day of HCl challenge. Respiratory system compliance, blood gas analysis and differential cell counts in a selective bronchoalveolar lavage (BAL) were determined 24 h after HCl. In a parallel experiment mice were observed for 14 days to assess epithelial damage and lung fibrosis.

Figure 1 TLQP-21 module lung inflammation and fibrosis. A) Lower neutrophil count in the BALF of the right bronchus at 24 hours after HCI. B) At day 14 lung compliance improved. C) Collagen deposition was lower in the mice treated with TLQP-21. * p 0.05.

1Universit degli Studi di Milano Bicocca, Department of Health Science, Monza, Italy

2015 Pozzi et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0

Web End =http:// http://creativecommons.org/licenses/by/4.0

Web End =creativecommons.org/licenses/by/4.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Pozzi et al. Intensive Care Medicine Experimental 2015, 3(Suppl 1):A562 http://www.icm-experimental.com/content/3/S1/A562

Page 2 of 2

Results

The treatment with TLQP-21 showed a significant decrease in the number of total cells in BALF, due to a lower recruitment of neutrophils at 24 hour after challenge with HCl, compared to the vehicle group (Figure 1A), with no differences in macrophage number , even if this did not translate in a functional improvement in lung compliance and oxygenation. At day 14 the TLQP-21 group showed an improvement in lung compliance (Figure 1B) and a decrease collagen deposition in lung tissue (Figure 1C).

Conclusion

TLQP-21 can decrease inflammatory response at an early phase in a mouse model of HCl-induced ARDS, which may modulate lung remodeling at a late phase, preventing a fibrotic evolution. Given these encouraging but not definitive results we aim to furtherassess the potential therapeutic effect of a higher dose of TLQP-21

Authors details

1Universit degli Studi di Milano Bicocca, Department of Health Science, Monza, Italy. 2Institut des Biomelecules Max Mousseron, Montpellier, France.

Published: 1 October 2015

doi:10.1186/2197-425X-3-S1-A562Cite this article as: Pozzi et al.: TLQP-21 modulate inflammation and fibrosis in a model of ards. Intensive Care Medicine Experimental 2015 3(Suppl 1):A562.

Submit your manuscript to a journal and benet from:

7 Convenient online submission7 Rigorous peer review7 Immediate publication on acceptance7 Open access: articles freely available onlihttp://www.springeropen.com/

Web End =ne 7 High visibility within the eld7 Retaining the copyright to your article

Submit your next manuscript at 7 http://www.springeropen.com/

Web End =springeropen.com