Discovering safe, novel immunomodulators that are effective in RA is currently a major therapeutic objective. Long-term immune system deviation is most striking in the host-parasite relationship, in which microbes may coexist with a human host. ES-62 exhibited powerful immunomodulation of CIA, preventing initiation of inflammatory arthritis. Crucially, ES-62 suppressed even established disease. These effects were due to inhibition of cytokine release, specifically TNF-α, and reversal of collagen specific Th1 responses associated with reduced expression of IFN-γ. The physiologic relevance of these observations was confirmed, as ES-62 down-regulated the release of proinflammatory cytokines (TNF-α and IL-6) from patient-derived samples.
- cytokine modulation
- articular inflammation