Natural killer cell anergy to cytokine stimulants in a subgroup of patients with heart failure: relationship to norepinephrine.

Heart failure is a disease characterized by chronically high levels of plasma norepinephrine and anergy in the cytotoxicity of circulating natural killer (NK) lymphocytes. This study shows that NK anergy extends to a significantly reduced cytotoxicity in response to the powerful NK stimulants, interleukin (IL)-2 and interferon (IFN)-alpha. Fifteen patients with heart failure, New York Heart Association stage III or IV, were studied for NK-cell-mediated cytotoxicity. The patients were divided into two groups based upon their NK cytotoxicity function: (1) those who had minimal baseline cytotoxicity and failed to respond following stimulation by IL-2 and IFN-alpha (n = 6), and (2) those who were about at the level of normal controls, and were responsive to IL-2 and IFN-alpha (n = 9). There was no relationship between the anergy and the etiology of the heart failure, laboratory indicators of heart failure, serum albumin or sodium, state anxiety, age or sex of the subjects. There was a statistically significant negative correlation between the response of NK cells to the stimulators IL-2 and IFN-alpha and the level of plasma norepinephrine in the heart failure patients. This was corroborated by in vitro testing of direct effects of norepinephrine on normal NK cells, which indicated that baseline cytotoxicity and the ability of these cells to respond to IL-2 were inhibited in a dose-dependent manner. The findings indicate that the NK cell anergy seen in heart failure patients extends to the response to the stimulators IL-2 and IFN-alpha in a subgroup of patients.