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 networ k of the immune system. These substances, referred to as cytokines, are imp ortantly involved in the highly regulated complex sequence of events of cel lular interaction that comprise immune responses. Atopic diseases, which af flict 20-30% of the general population, are now considered to be associated with a set of abnormal genetically regulated immune responses to foreign a ntigens, i.e., allergens. The atopic individual is characterized by the exc essive production of IgE antibody to allergens after inhalation, ingestion, and surface contact. There are now recognized over 19 major classes of cyt okines, which have been organized into the following categories according t o their major functional activities: 1) Acute phase reactants, promoting an d mediating natural immunity (e.g., IL-1, IL-6, TNF, interferons alpha and beta, and IL-8); 2) Cytokines that mediate cellular growth and differentiat ion (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 f actor); 4) Chemokines (alpha and beta major groups, DTG, RANTES); and 5) Cy tokines 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) consi ders atopy as a Th2-driven hypersensitivity reaction to allergens of comple x genetic and environmental origins, in which the Th1 lineage, normally dri ven by IL-2, TNF, and IFN-gamma is deficient, and in which a predominant Th 2 response is seen that is driven bg IL-4, IL-13, IL-5, and IL-IO. This kno wledge is finding application in both the diagnosis and therapy of allergic diseases, through the measurement or use of cytokines, which may replace d eficient quantities, or the use of anticytokines, which may neutralize elev ated quantities of cytokines, events that collectively contribute to the im munologic imbalance characteristic of the allergic state. In the future, th e application of cytokines will continue to find clinical application in al lergic disease, and it behooves the clinical allergist-immunologist to keep abreast of the exciting new developments that are occurring in this field.