Cytokines and allergic diseases: Clinical aspects

In recent years there has been an explosive expansion of knowledge relating to a family of proteins involved in the intercellular communication network of the immune system. These substances, referred to as cytokines, are importantly involved in the highly regulated complex sequence of events of cellular interaction that comprise immune responses. Atopic diseases, which afflict 20-30% of the general population, are now considered to be associated with a set of abnormal genetically regulated immune responses to foreign antigens, i.e., allergens. The atopic individual is characterized by the excessive production of IgE antibody to allergens after inhalation, ingestion, and surface contact. There are now recognized over 19 major classes of cytokines, which have been organized into the following categories according to their major functional activities: 1) Acute phase reactants, promoting and mediating natural immunity (e.g., IL-1, IL-6, TNF, interferons alpha and beta, and IL-8); 2) Cytokines that mediate cellular growth and differentiation (e.g., IL-7, IL-4, IL-2, IL-5, IL-10, IL-12, IL-13); 3) Cytokines that act as hematopoietic growth factors (IL-3, GMCSF, IL-9, IL-11, stern cell factor); 4) Chemokines (alpha and beta major groups, DTG, RANTES); and 5) Cytokines that exert lymphocyte regulatory activity (EG, IFN-gamma, TGF). Of particular importance to allergic disease is the recent recognition of the regulation of helper immune function by two lineages of T helper cells, i.e., Th1 and Th2, by these cytokines. The Th2 hypothesis of allergy (4) considers atopy as a Th2-driven hypersensitivity reaction to allergens of complex genetic and environmental origins, in which the Th1 lineage, normally driven by IL-2, TNF, and IFN-gamma is deficient, and in which a predominant Th2 response is seen that is driven bg IL-4, IL-13, IL-5, and IL-IO. This knowledge is finding application in both the diagnosis and therapy of allergic diseases, through the measurement or use of cytokines, which may replace deficient quantities, or the use of anticytokines, which may neutralize elevated quantities of cytokines, events that collectively contribute to the immunologic imbalance characteristic of the allergic state. In the future, the application of cytokines will continue to find clinical application in allergic disease, and it behooves the clinical allergist-immunologist to keep abreast of the exciting new developments that are occurring in this field.