Comparison of Plasma Levels of Cytokines and In Vitro Generation of Reactive Oxygen Species After Nicotine Infusion in Nicotine Users with Normal and Impaired Renal Function

Abstract

Several in vitro and animal studies suggest effects of nicotine on the immune system, but little evidence exists regarding the in vivo immunomodulation of nicotine in humans. The increased use of nicotine replacement therapy to aid smoking cessation claims further understanding of how nicotine affects blood leukocytes. This is of particular importance when nicotine therapy is used in diseases associated with alterations of the immune system, such as chronic renal failure. The present study evaluates the acute effects of nicotine infusion (NI) on some immunoregulatory functions in seven healthy subjects and seven patients with renal failure. All subjects were nicotine users and had refrained from using nicotine for 36 h before NI. Blood was collected before, immediately after, and 2 h after NI. Plasma concentrations of intercellular adhesion molecule-1 (ICAM-1) and the cytokines interleukin-2 (IL-2), IL-4, IL-10, interferon-γ and RANTES were measured using specific immunoassays. The generation of reactive oxygen species (ROS) induced by formyl-methionyl-leucyl-phenylalanine (fMLP), Ristocetin, adenosine 5′-diphosphate, or collagen was registered in whole blood as luminol-dependent chemiluminescence. Except for fMLP, these compounds induce leukocyte ROS generation by platelet mediated mechanisms. NI did not significantly affect the levels of the cytokines and ICAM-1 in any group. The peak and the persistent ROS production, induced by collagen and Ristocetin, was lower at some time points in patients with renal failure as compared to healthy subjects. Also in patients with renal failure, both peak height and persistent ROS generation induced by Ristocetin were reduced immediately after NI. Thus, nicotine inhibits some of the platelet-mediated activation of leukocyte ROS generation, and may be associated with platelet defects in renal failure.