Role of Cytokines in the Diagnosis of Asthma

Asthma is a chronic allergy symptomatic of the airways in the lungs and is characterized by excess mucous secretion, intermittent airflow obstruction and bronchial hyper-responsiveness. Inflammation can be triggered by dust, pollen, smoke, cold air, viral upper respiratory tract infection, other allergens leading to provocation of the bronchial airways and subsequent clinical manifestations. Additionally, atopy – the genetic predisposition for the development of an IgE mediated response to common environmental antigens is one of the most contributing factors towards development of asthma [1]. Of the varying degrees of infiltration by effector and mediator cells released during the airway inflammation, activated T-lymphocytes play a vital role by releasing a number of cytokines leading to asthma symptoms. The pathobiology, diagnosis and natural history of asthma management has called for elucidating the signaling pathways of cytokines as therapeutic and diagnostic targets.
Asthma or airway inflammation occurs due to an imbalance of Th1 and Th2 lymphocyte population in bronchial tissues. In general, Th1 is important in eliciting defense mechanisms in response to infection, produces cytokines like IL-2 and IFN-α.Overexpression of Th2 generates a host of cytokines like IL-4, IL-5, IL-6, IL-9, IL-13 and is critical to allergic inflammation [2]. Modification in the expression or structure of these cytokine genes, arising due to polymorphisms, results in a predisposition to generate asthma phenotypes. IL-1RA is secreted into the extracellular matrix by macrophages, monocytes, neutrophils in response to inflammation, polymorphisms reported in this IL-1 receptor antagonist is associated with severity in child and adult asthma. IL-2 plays a vital role in maturation of regulatory lymphocytes and in synthesis of cytokines and pro-inflammatory molecules. Two polymorphisms located in the promoter region of the IL-2 gene, in position -330, is related to atopic asthma. IL-4, the most widely studied gene for asthma and atopic diseases along with IL-13 enhances IgE production and its overexpression in the mast cells found in the airway of allergic patients.[3] ,[4] .IL-6 and IL-10 arrests cascade of inflammatory mediators and are present in reduced levels in macrophages and monocytes in bronchial tissues of asthma patients. IL-12β has been reported to be a studied candidate gene in asthma and has been implicated in childhood asthma. Single nucleotide polymorphisms (SNPs) in TGF-β has been associated with bronchial hyper-responsiveness and enhanced asthma susceptibility in patients with atopy [4] . Research into all the cytokines associated with asthma has however not transitioned from bench to clinic yet, inspite of successful preclinical trials, probably due to the heterogeneous nature of the disease. Therefore development of potential therapeutics based on neutralization of effector cytokines with limited range of defined activity holds promise compared to an approach based on blockade of cytokines [5].
In episodes of asthma, the presence of detectable chemokine profiles in bronchoalveolar lavage fluid (BALF), serum, sputum demonstrates a host of possible markers for the diagnosis of asthma and its phenotypes,[6] in patients with viral respiratory infection. Diagnostic approaches based on MRI and phage display techniques are still in the process of evaluation and may unravel the pathogenesis of the airway inflammatory disease.