Interleukin 3, Interleukin 5, and Granulocyte–Macrophage Colony‐Stimulating Factor

Several environmental stimuli and inflammatory mediators can induce the release of interleukin 3 (IL‐3), IL‐5, and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) from a number of myeloid and structural cells. These pleiotropic cytokines exhibit some overlapping effects because they share a common receptor β chain (βc) as well as several signal transduction pathways. While not required to maintain steady‐state hematopoiesis, they are important in pulmonary homeostasis and host defense against infections. Increased levels of these cytokines are present in the airway of asthmatics, and experimental studies have demonstrated the contribution of IL‐3, IL‐5, and GM‐CSF to the development, maintenance, and exacerbation of airway immune inflammatory responses to allergens. However, therapeutic targeting of these βc‐engaging cytokines in humans faces substantial challenges and, in the case of IL‐5, studies have yielded limited results. The identification of asthma phenotypes regulated by specific cellular and molecular pathways may invigorate the potential of selective inhibition of IL‐3, IL‐5, and/or GM‐CSF in certain asthmatic individuals.