Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment

Abstract

N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione, has been in clinical use for more than 30 yrs as a mucolytic drug. It has also been proposed for and/or used in the therapy and/or prevention of several respiratory diseases and of diseases involving an oxidative stress, in general. The objective of the present study was to evaluate the effect of long-term treatment with NAC on influenza and influenza-like episodes.A total of 262 subjects of both sexes (78% ≥65 yrs, and 62% suffering from nonrespiratory chronic degenerative diseases) were enrolled in a randomized, doubleblind trial involving 20 Italian Centres. They were randomized to receive either placebo or NAC tablets (600 mg) twice daily for 6 months. Patients suffering from chronic respiratory diseases were not eligible, to avoid possible confounding by an effect of NAC on respiratory symptoms.NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group. Frequency of seroconversion towards A/H 1 N 1 Singapore 6/86 influenza virus was similar in the two groups, but only 25% of virus-infected subjects under NAC treatment developed a symptomatic form, versus 79% in the placebo group. Evaluation of cell-mediated immunity showed a progressive, significant shift from anergy to normoergy following NAC treatment.Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals. N-acetylcysteine did not prevent A/H 1 N 1 virus influenza infection but significantly reduced the incidence of clinically apparent disease. Eur Respir J 1997; 10: 1535-1541

Antioxidant Therapy as a Potential Approach to Severe Influenza-Associated Complications

“…The authors concluded that NAC did not prevent influenza A (H1N1) virus infection, but did significantly reduce the incidence of clinically apparent disease [52]. In another paper, it has been reported that a patient with viral pneumonia caused by the novel influenza A (H1N1) virus 2009 infection and septic shock improved rapidly after continuous intravenous infusion of high-dose NAC at 100 mg/kg combined with oseltamivir [53].…”

N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial

“…NAC stimulates glutathione synthesis and scavenges free radicals. 11 This compound is taken up by N-deacetylase, hydrolyzed to form cysteine and is used for glutathione synthesis. 12 Afterwards, glutathione peroxidase enzyme family, particularly glutathione peroxidase-1, utilizes glutathione to protect cells from oxidative damage.…”

Impact of 30-Day Oral Dosing with N-acetyl-l-cysteine on Sprague-Dawley Rat Physiology

“…NAC freatinent is correlated with an increase in T cell immunity (Breithaupt et al, 1996;Droge, Eck, and Mihm, 1992;Wu, Levy, and Black, 1989) and may provide therapeutic benefit for a wide range of diseases (Beloqui et al, 1993;Bengtsson et al, 2001;De Flora, Grassi, and Carati, 1997;Walters et al, 1986) possibly by modulating immune response. Intravenous adminisfration of large doses of NAC as an antidote for acetaminophen poisoning can cause anaphylactic responses in sensitive individuals (Lifshitz, Kommehl, and Reuveni, 2000;Reynard, Riley, and Walker, 1992) most likely due to histamine release (Lifshitz, Kommehl, and Reuveni, 2000).…”

“…Acute side-effects reported in association with NAC administration range from gastrointestinal upset, vomiting, and fatigue to anaphylactic and allergic reactions (Bobb, Arfsten, and Jederberg, 2004;Pendyala et al, 2001;Pendyala and Creaven, 1995;Tenenbein, 1984;Ziment, 1988). Several studies have reported on the sideeffects in patients administered high doses of NAC (De Flora, Grassi, and Carati, 1997;De Rosa et al, 2000;Lifshitz, Kommehl, and Reuveni, 2000;Pendyala et al, 2001;Pendyala and Creaven, 1995;van Zandwijk et al, 2000), but the subject populations in most of these studies are patients with serious medical conditions. Therefore, the symptoms reported m these studies may not represent side-effects expected to occur in healthy populations under similar dosing regimens.…”