Interleukin-4 and Cardiac Fibrosis in Patients With Heart Failure

Interleukin-4 (IL-4) stimulates inflammatory responses, activates collagen synthesis, promotes fibrosis progression, and inhibits the production of inflammatory cytokines. We studied the relationship between the urinary IL-4 level and levels of markers of cardiac fibrosis and left ventricular volume in 98 patients with heart failure (HF). The left ventricular end-systolic volume index (LVESVI) and left ventricular end-diastolic volume index (LVEDVI) were calculated, and IL-4, tumor necrosis factor-alpha (TNF-alpha), IL-6, and aminoterminal propeptide of procollagen type III (PIIINP) levels were recorded.Comparison of urinary IL-4 and PIIINP levels in patients and control subjects gave values of 12 (12) pg/mL and 4 (3) pg/mL (P<.0001), respectively, and 5 (2) ng/mL and 4 (1) ng/mL (P<.0001), respectively. The IL-4 level correlated with LVESVI and LVEDVI (r=-0.22, P<.05), and with PIIINP (r=0.24, P<.05). In patients with hypertensive cardiomyopathy, there was a good correlation between IL-4 and PIIINP levels (r=0.7, P<.01). Correlations were also observed between IL-4 and TNF-alpha (r=0.3, P<.01) and IL-6 (r=0.5, P<.0001).The urinary IL-4 level correlated with cardiac fibrosis and remodeling in patients with HF. The relationship was stronger in those with hypertensive cardiomyopathy.

La interleucina 4 (IL-4) estimula la respuesta inflamatoria, activa la síntesis de colágeno, promueve la progresión de fibrosis e inhibe la producción de citocinas inflamatorias. Estudiamos las concentraciones urinarias de IL-4, su relación con los marcadores de fibrosis miocárdica y con los volúmenes del ventrículo izquierdo en 98 pacientes con insuficiencia cardiaca. Calculamos el índice de volumen telesistólico (IVTS) y telediastólico (IVTD), los valores de IL-4, factor de necrosis tumoral (TNF) alfa, IL-6 y propéptido aminoterminal del procolágeno tipo III (PIIINP).Comparamos los valores urinarios de IL-4 y PIIINP en pacientes y controles (12 ± 12 frente a 4 ± 3 pg/ml, p < 0,0001 y 5 ± 2 frente a 4 ± 1 ng/ml, p < 0,0001). La IL-4 se correlacionó con IVTS e IVTD (r = -0,22; p < 0,05) y con PIIINP (r = 0,24; p < 0,05). En la cardiopatía hiperten-siva encontramos una correlación entre IL-4 y PIIINP (r = 0,7; p < 0,01). Correlacionamos la IL-4 con TNF-α y la IL-6, obteniendo r = 0,3, p < 0,01 y r = 0,5, p < 0,0001.La IL-4 en orina se relaciona con la fibrosis miocárdica y el remodelado en la insuficiencia cardiaca. La relación es mayor en la cardiopatía hipertensiva.