cells to Mediastinal lymph nodes while increasing the egress of immature dendritic cells away from the lung. These effects resulted in a decrease in allergen-induced responses of the cells mediating allergic reactivity, TH-2 cells. These IP-induced responses likely contribute to its apparent function in inhibiting certain mouse inflammation responses as exemplified by the failure of IP receptor deficient mice to develop full lung airway allergic responses to ovalbumin in a model of allergic inflammation. In human studies, PGI2 failed to alter bronchoconstriction responses to allergen but did protect against exercise-induced and ultrasonic water-induced bronchoconstriction in asthmatic patients. It also caused bronchodilation in two asthmatic patients. However, these studies were done before the availability of potent and selective IP agonists. These agonists might produce more effective inhibitor results on airways allergic diseases but their toxicity (e.g. pulmonary edema, hypotension) has tended to restrict there study in asthmatic patients. IP receptors also appear involved in suppressing non-allergic inflammatory responses. IP receptor-deficient mice exhibit a reduction in the extent and progression of inflammation in a model of collagen-induced arthritis. This effect may result from regulating the expression of arthritis-related, pro-inflammatory genes (i.e. those for IL-6, VEGF-A, and RANKL). On the other hand, IP receptors may serve to promote non-allergic inflammatory responses: IP receptor-deficient mice exhibited increased lung inflammation in a model of bleomycin-induced pulmonary fibrosis while mice made to over-express the PGI2-forming enzyme, Prostacyclin synthase, in their airway epithelial cells were protected against lung injury in this model. Pain perception IP(-/-) mice exhibit little or no writhing responses in an acetic acid-induced pain model. The mouse IP receptor also appears to be involved in the development of heat-induced hyperalgesia. These and further studies using IP receptor antagonists in rats indicate that IP receptors on pain-perceiving sensory neurons of the dorsal root ganglia as well as on certain neurons in the spinal cord transmit signals for pain, particularly pain triggered by inflammation. Clinical significance Toxicity IP receptor agonists, particularly when used intravenously, have been associated with the rapid development of pulmonary edema, hypotension, bleeding due to inhibition of platelet aggregation, and tachycardia. Clinical use of these agonists is contraindicated in patients suffering many conditions. For example, the IP agonist iloprost is contraindicated in patients with unstable angina; decompensated cardiac failure (unless under close medical supervision); severe cardiac arrhythmias; congenital or acquired heart valve defects; increased risk of bleeding; a history of myocardial infarction in