Recurrent airway obstruction (RAO) or heaves is a common, severe, debilitating respiratory condition of horses characterized by profound airway neutrophilia, reversible bronchospasm and excessive mucus production. The disorder shares many clinical and pathological features of severe persistent asthma in humans. The equine disease has a genetic component but this is not linked to the MHC. Although the pathogenesis of the disease is unknown, it is widely believed to involved a dysregulation of the immune system. The molecular mechanisms of RAO have not yet been determined. Using the techniques of quantitative real time PCR, the cytokine mRNA profiles in the bronchoalveolar lavage lymphocytes, macrophages and neutrophils and in the blood mononuclear cells of control (n=12) and RAO-affected (n=12) horses will be assayed when horses are asymptomatic; during the acute phases of the disease (5 hrs, 24 hrs); during the chronic phase of the disease (3 weeks); and during the natural and/or pharmacologically-induced remission phases. The specific mRNA levels that will be assayed include the Th-1 (IL-12, IL-2, Interferon-gamma) and Th-2 (IL-4, IL-5, IL-10) associated cytokines. By studying these time points, it will be determined (1) if asymptomatic horses can be identified prior to development of the disease; (2) if the acute and chronic phases of the inflammatory disease reflect the same mechanisms-e.g. a Th-1 or Th-2 bias; and (3) if the molecular events associated with natural remission of the pulmonary inflammation are dissimilar from those occurring with corticosteroid administration in either the equine of human airway. This study will benefit both humans and horses by providing an understanding of the cytokine profiles and molecular events involved in inciting and propagating the pulmonary neutrophilia associated with reversible airway obstruction.
