Changes in the pro-inflammatory cytokine production and peritoneal macrophage function in rats with chronic heart failure

Chronic heart failure (CHF) is a state of immune activation, and pro-inflammatory cytokines play an important role in its development and progression. Macrophages (Mϕs), when activated, are the main source of pro-inflammatory cytokines. We measured interleukin-6 (IL-6), interleukin (IL-1β) and tumor necrosis factor - α (TNF-α) production after lipopolysaccharide (LPS)-stimulation, as well as peritoneal Mϕs migration, phagocytic capacity, chemotaxis index, and hydrogen peroxide production, in an attempt to clarify the role of this cell in an animal model of CHF. Ligature of the left coronary artery or sham operation was performed in adult Wistar rats. After 12 weeks, resident and total cell number, phagocytic capacity, chemotaxis index, and hydrogen peroxide production in Mϕs were significantly higher in CHF than in control rats. The production of IL-6 and TNF- α was similarly significantly enhanced in CHF as compared with controls. Mϕs obtained from CHF rats were more responsive to LPS, suggesting the existence, in vivo, of possible factor(s) modulating the production of pro-inflammatory cytokines. The results demonstrated that there is modification of peritoneal Mϕs function along CHF development, possibly contributing to the pathophysiological process in the establishment of CHF.