Milara, JavierRoger Laparra, InésMontero Magalló, PaulaArtigues, EnriqueEscrivá, JuanRío, Raquel delCortijo, Julio2024-05-302024-05-302024Milara, J., Roger, I., Montero, P., Artigues, E., Escrivá, J., Del Río, R., & Cortijo, J. (2024). Targeting IL‐11 to reduce fibrocyte circulation and lung accumulation in animal models of pulmonary hypertension‐associated lung fibrosis. British Journal of Pharmacology, bph.16393. https://doi.org/10.1111/bph.163930007-11881476-5381http://hdl.handle.net/11268/12875Background and Purpose: IL-11 is a member of the IL-6 family of cytokine initially considered as haematopoietic and cytoprotective factor. Recent evidence indicates that IL-11 promotes lung fibrosis and pulmonary hypertension in animal models and is elevated in lung tissue of patients with pulmonary fibrosis and pulmonary hypertension. Fibrocytes are bone marrow-derived circulating cells that participate in lung fibrosis and pulmonary hypertension, but the role of IL-11 on fibrocytes is unknown. We investigated the role of IL-11 system on fibrocyte activation in different in vitro and in vivo models of lung fibrosis associated with pulmonary hypertension. Experimental Approach: Human fibrocytes were isolated from peripheral blood of six healthy donors. Recombinant human (rh)-IL-11 and soluble rh-IL-11 receptor, α subunit (IL-11Rα) were used to stimulated fibrocytes in vitro to measure:- cell migration in a chemotactic migration chamber, fibrocyte to endothelial cell adhesion in a microscope-flow chamber and fibrocyte to myofibroblast transition. Mouse lung fibrosis and pulmonary hypertension was induced using either IL-11 (s.c.) or bleomycin (intra-tracheal), while in the rat monocrotaline (intra-tracheal) was used. In vivo siRNA-IL-11 was administered to suppress IL-11 in vivo. Key Results: RhIL-11 and soluble rhIL-11Rα promote fibrocyte migration, endothelial cell adhesion and myofibroblast transition. Subcutaneous (s.c.) IL-11 infusion elevates blood, bronchoalveolar and lung tissue fibrocytes. SiRNA-IL-11 transfection in bleomycin and monocrotaline animal models reduces blood and lung tissue fibrocytes and reduces serum CXCL12 and CXCL12/CXCR4 lung expression. Conclusion and Implications: Targeting IL-11 reduces fibrocyte circulation and lung accumulation in animal models of pulmonary hypertension-associated lung fibrosis.enghttps://creativecommons.org/licenses/by-nc/4.0/Factores de crecimiento de FibroblastosFibrosis pulmonarHipertensión pulmonarjournal article10.1111/bph.16393open accessAparato respiratorioEnfermedadCélulaAttribution-NonCommercial 4.0 InternationalGoal 3: Ensure healthy lives and promote well-being for all at all ages