**1. Influenza**

Influenza is an acute infectious disease that exerts a very great effect on human society, causing huge medical and economic losses. Influenza usually occurs in annual seasonal (winter) outbreaks or epidemics (in moderate temperature climates). Moreover, influenza pandemics periodically attack the populations of all continents. People of all ages are affected, but the prevalence is greatest in school-age children. The disease's severe course, complications, and

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

mortality are greatest in infants, the elderly, and those with underlying illnesses—chronic pulmonary or cardiovascular diseases, and diabetes mellitus. The severe complications include hemorrhagic bronchitis or pneumonia (primary viral or secondary bacterial). In addition, fulminant fatal influenza viral pneumonia can occur, with death proceeding in as little as 48 hours after the initial flu symptoms [1]. The World Health Organization recommends influenza vaccines as a main tool for preventing infection and anti-influenza chemotherapeutics with antiviral drugs for treatment and/or prophylactically [1]. The antivirals effective against influenza are divided into two types based on their modes of action: (i) inhibitors of the neuraminidase—oseltamivir, zanamivir, peramivir, and related compounds, efficacious against influenza A and B virus infections, and (ii) blockers of the protein M2—rimantadine-HCl and amantadine-HCl, active against influenza virus A infections. Although both types of agents have proven antiviral effectivity, the rate of drug resistance is constantly increasing, especially for M2 blockers [2].

with concomitant attainment of the mucus glands. Small- and medium-sized bronchioles are strongly affected by the processes seen in the larger airways, with an entirely necrotic bronchiolar wall associated with polymorphonuclear cell infiltrate. Influenza virus pneumonia very often proceeds to secondary bacterial pneumonias. Destruction of alveolar epithelium

Lung disorders in influenza virus infection may be triggered by: (i) a massive infiltration of leukocytes, mainly polymorphonuclear leukocytes, into the alveolar space; (ii) a decrease in the partial pressure of oxygen, causing the development of hypoxia; (iii) an increase in the

release of cytokines, eicosanoids and prostaglandin E2 and an enhanced immune response;

Our previous data and that of most of the literature showed that experimental influenza virus infection in susceptible laboratory animals (mice and ferrets) imitates the above influenza clinical picture: progressive damage of the alveolar cells, acute inflammatory reaction, and development of massive bronchitis and probably pneumonia, in parallel with a decrease in endogenous lipid- and water-soluble antioxidants levels, as well as the compensatory changes

Lungs are the target organs of the influenza virus. However, in the course of influenza virus infection, dynamic changes in oxidative metabolism, provoked by the overgeneration of ROS (reactive oxygen species) and the activation of neutrophils, can reach the development of oxidative stress [5, 18, 19, 22–24]. Oxidative stress is defined as a disturbance of the prooxidant-antioxidant balance in favor of prooxidants. Influenza viruses are known to induce ROS-generating enzymes and to disturb antioxidant defenses [5, 18, 19, 25], causing changes in antioxidant enzyme activity [5] and decreases in endogenous low-molecular-weight antioxidants. Overgeneration of ROS may influence signaling pathways by activating "redox switches" [26]. In lungs, redox homeostasis is crucial in the pathology of influenza because it is associated with cytokine production, inflammation, cell death, and other pathological

Since the products of oxidative stress possess high cytotoxic activity, it is very important to study mechanisms of detoxification in the infected body. After the epithelial cells are infected, tissue-resident alveolar macrophages are the first responders to viral infection in the lungs (**Figure 1**). They can promote viral clearance through the phagocytosis of viral particles or infected apoptotic cells (efferocytosis) and the release of a plethora of inflammatory cytokines and chemokines to initiate and drive the immune response [27–30] . Due to the ability of ROS to react with almost any kind of biological molecule, including proteins, lipids, and nucleic acids, their elevation is generally associated with genome instability, dysfunction of organelles, and

Antioxidant defense mechanisms, including enzymes like superoxide dismutase, catalase, and small molecules such as vitamins C and E and glutathione, protect tissues against oxidants [32].

processes that could be triggered by enhanced ROS generation (**Figure 1**).

and development of metabolic acidosis; (iv) a "cytokine storm"—a

Vitamin E and Influenza Virus Infection http://dx.doi.org/10.5772/intechopen.80954 69

and endothelium can worsen the severity of lung injury [4, 15].

and (v) the development of oxidative stress [5, 7, 16, 17].

of antioxidant enzyme activities [18–21].

**2.2. Oxidative stress in influenza virus infection**

partial pressure of CO2

apoptosis [31].

Two principal problems are related with vaccine prevention: (i) anti-influenza vaccines commonly demonstrate 70–90% effectivity in young persons, with rates markedly decreasing in the elderly; (ii) the protection length is limited to a few months or a season because of the continuous viral antigenic drift based on gradually accumulated mutations, requiring annual revaccination [3].
