A Prostacyclin Analog, Cicaprost, Exhibits Potent Anti-Inflammatory Activity in Human Primary Immune Cells and a Uveitis Model

Purpose: To investigate the therapeutic potential of a prostacyclin (IP) receptor agonist for ocular inflammation and the effect on immune cells. Methods: The anti-inflammatory activities of cicaprost were determined in primary human monocyte-derived macrophages and human monocyte-derived dendritic cells (MoDC), as well as a lipopolysaccharides (LPS)induced rat uveitis model. Multiple cytokine release was measured by utilizing Luminex Technology. Prostacyclin (IP) Receptor expression was detected by reverse transcription-polymerase chain receptor. Leukocyte infiltration and protein exudation in the rat uveitis model were measured using a hemocytometer and protein concentration by a NanoDrop instrument. Results: Cicapost, an IP receptor agonist, potently inhibits proinflammatory chemokines/cytokine production not only from LPS-or TNF alpha (tumor necrosis factor-alpha)-induced primary human monocyte-derived macrophages, but also from LPS-stimulated MoDC. While constitutively expressed in macrophages, the IP receptor was inducible by LPS stimulation in MoDCs. In a LPS-induced rat uveitis model, cicaprost efficaciously prevents ocular inflammatory cell and protein leakage, as well as inflammatory cytokine release. Conclusion: The IP receptor agonist cicaprost is a potent anti-inflammatory agent, implicating that the tightly controlled PGI(2)/IP signaling pathway is important in regulating inflammation. This response could be harnessed in ocular inflammatory disease where steroids are currently the standard of care.