Understanding modulation of the host immune system by pathogens offers rich therapeutic potential. Parasitic filarial @entity2199 are often tolerated in @entity1 hosts for decades with little evidence of pathology and this appears to reflect parasite-induced suppression of host proinflammatory immune responses. Consistent with this, we have previously described a filarial @entity2199 -derived, secreted @entity2945 -containing glycoprotein, ES-62, with immunomodulatory activities that are broadly anti-inflammatory in nature. We sought to evaluate the therapeutic potential of ES-62 in vitro and in vivo in an @entity792 model, namely, collagen-induced @entity625 in DBA/1 @entity19 . ES-62 given during collagen priming significantly reduced @entity625 . Crucially, ES-62 was also found to suppress collagen-induced @entity625 severity and progression when administration was delayed until after clinically evident disease onset. Ex vivo analyses revealed that in both cases, the effects were associated with inhibition of collagen-specific pro-inflammatory/Th1 cytokine (TNF-alpha, IL-6, and IFN-gamma) release. In parallel in vitro @entity1 tissue studies, ES-62 was found to significantly suppress macrophage activation via cognate interaction with activated T cells. Finally, ES-62 suppressed LPS-induced @entity309 synovial TNF-alpha and IL-6 production. Evolutionary pressure has promoted the generation by pathogens of diverse mechanisms enabling host immune system evasion and induction of "tolerance." ES-62 represents one such mechanism. We now provide proof of concept that parasite-derived immunomodulatory strategies offer a novel therapeutic opportunity in @entity625 .

A novel therapeutic approach targeting articular inflammation using the filarial @entity2199 -derived XXXX -containing glycoprotein ES-62.

@entity1 :: ('9606', 'Species') :: ['human'] @entity2199 :: ('6239', 'Species') :: ['nematode', 'nematodes'] @entity625 :: ('MESH:D001168', 'Disease') :: ['initiation of inflammatory arthritis', 'inflammatory arthritis', 'arthritis'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity2945 :: ('MESH:D010767', 'Chemical') :: ['phosphorylcholine'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmune disease'] @entity309 :: ('MESH:D001172', 'Disease') :: ['rheumatoid arthritis']
@entity2945 :: (MESH:D010767,Chemical) :: ['phosphorylcholine']
