Lung Mediators Of Leukocyte Infiltration And Activation In Chronic Heart Failure Patients

RationaleUsing a rat myocardial infarction model of CHF we have found fibrotic reinforcement of the extracellular matrix which results in tissuestiffening and an increase in alveolar type II cells and surfactant which provides homeostatic compensation that normalises lungmechanics (1). Emerging evidence suggests that this pulmonary remodelling may be regulated by two distinct phenotypes of pulmonarymacrophages; M1 granulocyte-macrophage colony stimulating factor (GM-CSF) stimulated alveolar macrophages, and M2 monocytechemotactic protein (MCP)-1 stimulated, interstitially derived macrophages. In the rat we found a 4.5-fold increase in bronchoalveolarlavage (BAL) MCP-1, corresponding to a 3-fold increase in recruited macrophages (1) with no detectable GM-CSF. A subsequent clinicalstudy demonstrating a 3-fold increase in circulating CD11b monocytes in CHF patients which correlated with disease severity providedhifurther evidence of M2 predominance in this population (2). To examine potential mediators of lung leukocyte infiltrate in BALObjective:from CHF patients compared to non-CHF controls. Clinical samples were obtained via mini-BAL (60ml) from CHF (n=7) andMethods:non-CHF (n=11) patients immediately prior to coronary artery bypass surgery at Flinders Medical Centre, Adelaide, South Australia. : CHF patients demonstrated a 4-fold increase in BAL M2 mediator, MCP-1 (2641(766-4115) versus controls 558(277-940) pg/mlResultsepithelial lining fluid (ELF) (median (25-75 percentiles); p=0.03). No difference in BAL M1 mediator, GM-CSF (10(0-35) versus 12(0-22)ththpg/ml ELF; p=0.46) or in the neutrophil chemoattractant IL-8 (6.68(1.68-35.16) versus 2.89(0.95-7.29) ng/ml ELF; p=0.47) was found. Therewas no relationship between BAL and plasma MCP-1 (r=0.051; p=0.35) suggesting a lung source with resultant alveolar chemotactic2gradient. This was reflected in a smaller patient cohort for whom BAL cell counts were available (n=3/group) which indicated an 8-foldincrease in predominantly macrophages in the lungs of CHF patients. : These human studies support our findings in the ratConclusionmyocardial infarct model of CHF and may be suggestive of an M2 dominant alveolar macrophage prevalence in the lung in CHF.