Relationship between Serum Level Indoleamine 2, 3-Dioxygenase (IDO) and Level of Asthma Control in Patients with Allergic Bronchial Asthma

Abstract

Bronchial Asthma is a disease with multifactor etiology (Ito et al., 2006). Asthma is defined by the global and initiative for asthma management and prevention GINA as chronic inflammatory disorder affecting the airways, in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyper responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness particularly at night or in the early morning (GINA 2012). The IDO pathway has been found to contribute substantially to the control of allergic inflammation. Traditionally recognized for its immunomodulatory role in infection, pregnancy, autoimmunity and current data suggest that a normal induction of IDO activity, which decreases serum tryptophan levels and increases the levels of trp metabolites, controls the allergic inflammation (Pietras et al., 2011). Trp is an essential starting point of two biochemical pathways: (i) the enzyme tryptophan 5-hydroxylase converts trp into 5-hydroxytryptophan, which is subsequently decarboxylized to 5-hydroxytryptamine (5-HT, serotonin), an essential neurotransmitter and vasoconstrictor, and (ii) two atoms of the molecular oxygen are inserted into L-trp to form N-formylkynurenine, the first and rate-limiting step in the kynurenine pathway thus causing depletion of tryptophan which causes halted growth of microbes as well as Tcells. (Grohmann et al., 2003). Indoleamine 2,3dioxygenase (IDO) is an enzyme that mediates tryptophan catabolism into its metabolites including kynurenine or quinolinic acid. IDO protein is widely expressed in a variety of cell types including B cells, macrophages, eosinophils, dendritic cells (DCs), endothelial cells, and many types of tumor cells (Beutelspacher et al., 2006). Because products of tryptophan metabolism are required for normal cell growth, depletion of IDO adversely impacts cell function (Mellor, 2005). In the last decade, IDO has emerged as an important negative regulator in the immune system primarily because of its function in DCs, which play a quintessential role in antigen presentation to T cells (Munn, 2006). Formation of trp metabolites rather than trp deprivation itself seems to establish tolerance toward allergens (Moingeon et al., 2006). The activity of IDO seems to positively modify the inflammatory state of atopy or allergy. The tryptophan degradation pathway is important for tolerance induction which establishes the IDO pathway as central to allergic inflammation (Von Bubnoff and Bieber 2012). Other studies have established IDO as a proinflammatory enzyme. The aim of this study was to determine the relationship between serum level IDO and the level of asthma control in atopic patients with allergic bronchial asthma. This study was a cross-sectional study performed on 40 atopic patients with allergic bronchial asthma attending the Allergy and Immunology Clinic of Ain Shams University Hospitals. Asthma diagnosis was established according to GINA) recommendations 2012, based on clinical asthma symptoms and lung function tests. The level of asthma severity and control was determined on the basis of GINA Report Guidelines (GINA, 2012). Results clearly show there is a large difference between IDO levels in controlled asthma patients’ versus normal subjects. There was a large difference between IDO levels in uncontrolled asthma patients’ versus normal subjects. Therefore serum level IDO is higher in patients with allergic bronchial asthma when compared to normal persons. However, upon comparing IDO levels between group I and group II i.e. between patients with controlled and uncontrolled asthma the difference is not statistically significant. So there was no relation between clinical asthma severity and IDO level. In conclusion, we postulate the possible role of IDO in bronchial asthma as a proinflammatory mediator (regardless of level of asthma control) with significant rise in IDO level, but there was no correlation between its level and severity of symptoms. The current challenge is to exactly identify the mechanisms and outcomes between the IDO pathway and allergy-related immune functions as different researchers use different systems in the complex field of atopy (Von Bubnoff and Bieber 2012), which explain why there is a debate about the role of IDO in allergy. IDO expression has been known to increase when inflammation occurs as a consequence of normal tissue function to protect tissues from collateral damage and facilitate tissue healing (Mellor 2005). There have been contradictory results as to whether IDO acts as pro-inflammatory or tolerogenic enzyme in allergy. Most experiments where done on mice which may behave differently than human IDO. So the association between the expression of IDO activity and airway inflammation in human asthma has not yet been adequately investigated, as few studies have been done on bronchial asthma on animal or human subjects.