A novel therapeutic approach to cytokine modulation in articular inflammation using filarial nematode derived ES-62
© The Author(s) 2003
Received: 14 January 2003
Published: 24 February 2003
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.
We have investigated our previously discovered filarial derived ES-62 for therapeutic potential in RA.
ES-62 was administered during collagen-induced arthritis (CIA) either at immunization (prophylactic) or 24 hours after the onset of clinically evident disease (therapeutic). Cytokine and antibody responses were measured in ex vivo cultures. RA synovial cultures were also made.
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.
The host–parasite relationship has long promised therapeutic potential. Our data clearly show that ES-62, a filarial-derived moiety, can profoundly alter cytokine expression in vitro and in vivo in inflammatory arthritis. This in turn suggests an intriguing role for ES-62 in treating chronic inflammatory diseases. Finally, our data have implications for the mechanisms that might underpin previously reported epidemiologic interactions between chronic infection and autoimmunity.