Abstract
HE3286 is a novel synthetic steroid that limits acute and chronic inflammation in rodents. HE3286 limited carrageenan‐induced pleurisy, LPS‐induced NFkB activation, and TNFa and IL‐6 levels. Oral HE3286 treated established disease in models of adjuvant and collagen‐induced arthritis, experimental autoimmune encephalitis, ulcerative colitis, and collagen antibody‐induced arthritis. Dose dependent reductions were seen in disease score and levels of pro‐inflammatory cytokines including IL‐6. Unlike corticosteroids, HE3286 was not immune suppressive in classical models, including human MLR and mitogen induced lymphocyte proliferation, murine DTH, OVA immunization, and reporter antigen popliteal lymph node assays. HE3286 is currently in Phase I/II trials in patients with chronic inflammatory conditions. By possibly mimicking a key component of the body's own natural hormonal system, HE3286 may reverse acute inflammation and prevent the transition to chronic disease. This approach may be a breakthrough in treating inflammatory diseases.
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