Importance of cytokines in murine allergic airway disease and human asthma.
Asthma is a common, disabling inflammatory respiratory disease that has increased in frequency and severity in developed nations. We review studies of murine allergic airway disease (MAAD) and human asthma that evaluate the importance of Th2 cytokines, Th2 response-promoting cytokines, IL-17, and proinflammatory and anti-inflammatory cytokines in MAAD and human asthma. We discuss murine studies that directly stimulate airways with specific cytokines or delete, inactivate, neutralize, or block specific cytokines or their receptors, as well as controversial issues including the roles of IL-5, IL-17, and IL-13Ralpha2 in MAAD and IL-4Ralpha expression by specific cell types. Studies of human asthmatic cytokine gene and protein expression, linkage of cytokine polymorphisms to asthma, cytokine responses to allergen stimulation, and clinical responses to cytokine antagonists are discussed as well. Results of these analyses establish the importance of specific cytokines in MAAD and human asthma and have therapeutic implications.
Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA. finkelman@pol.net
Fred D
FD
Finkelman
Simon P
SP
Hogan
Gurjit K Khurana
GK
Hershey
Marc E
ME
Rothenberg
Marsha
M
Wills-Karp
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D051379:Mice; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy
D000485:Allergens; D016207:Cytokines; D018836:Inflammation Mediators