Impaired norepinephrine regulation of monocyte inflammatory cytokine balance in heart failure

AIM: human monocytes and monocytic THP-1 cells. METHODS: mol/L or neither (control) for 4 h. Tumor necrosis factor-alpha (TNFα) and interleukin-10 (IL-10) production were determined by ELISA. Relative contribution of α- and β-adrenergic receptor subtypes on immunomodulatory activity of NE was assessed in LPS-stimulated THP-1 cells incubated with NE, the α-selective agonist phenylephrine (PE), and the β-selective agonist isoproterenol (IPN). NE-pretreated THP-1 cells were also co-incubated with the β-selective antagonist propranolol (PROP), α2-selective antagonist yohimbine (YOH) or the α1-selective antagonist prazosin (PRAZ). RESULTS: 0.012). In THP-1 cells, NE and IPN, but not PE, induced a dose-dependent suppression of TNFα. Co-incubation with NE and antagonists revealed a dose-dependent inhibition of the NE suppression of TNFα by PROP, but not by YOH or PRAZ. Dose-dependent increases in IL-10 production were seen with NE and IPN, but not with PE. This effect was also antagonized by PROP but not by YOH or PRAZ. Pretreatment of cells with IPN attenuated the effects of NE and IPN, but did not induce a response to PE. CONCLUSION: NE regulation of monocyte inflammatory cytokine production may be reduced in moderate-severe HF, and may be mediated through β-adrenergic receptors.