The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis.
OBJECTIVE
In countries where parasitic infections are endemic, autoimmune disease is relatively rare, leading to the hypothesis that parasite-derived immunomodulators may protect against its development. Consistent with this, we have previously demonstrated that ES-62, a 62 kDa phosphorylcholine (PC)-containing glycoprotein that is secreted by filarial nematodes, can exert anti-inflammatory action in the murine collagen-induced arthritis (CIA) model and human rheumatoid arthritis-derived synovial tissue cultures. As a first step to developing ES-62-based drugs, the aim of this study was to determine whether the PC-moiety of ES-62 was responsible for its anti-inflammatory actions.


METHODS
We compared the anti-inflammatory activity of a PC-free form of recombinant ES-62 (rES-62) and a synthetic PC-ovalbumin conjugate (OVA-PC) with that of native ES-62 in the CIA model and synovial tissues from patients with rheumatoid arthritis.


RESULTS
The anti-inflammatory actions of ES-62 in CIA appear to be dependent on the PC moiety as indicated by the reduction in severity of disease and also suppression of collagen-specific T helper 1 cytokine production observed when testing OVA-PC, but not rES-62. Interestingly, the anti-inflammatory activity of PC did not correlate with a reduction in anti-collagen IgG2a levels. Also, the ES-62-mediated suppression of interferon-gamma from human patient tissues could be mimicked by OVA-PC but not rES-62 or ovalbumin.


CONCLUSIONS
In countries where filariasis is endemic the reduced detection of inflammatory diseases, such as rheumatoid arthritis may be because of the anti-inflammatory action of the PC moieties of ES-62. PC may thus provide the starting point for the development of novel, safe immunomodulatory therapies.
Harnett
M M
MM
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK.
Kean
D E
DE
Boitelle
A
A
McGuiness
S
S
Thalhamer
T
T
Steiger
C N
CN
Egan
C
C
Al-Riyami
L
L
Alcocer
M J
MJ
Houston
K M
KM
Gracie
J A
JA
McInnes
I B
IB
Harnett
W
W
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010767:Phosphorylcholine / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D013583:Synovial Membrane / Q000276:immunology; D046509:Tissue Culture Techniques
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D010767:Phosphorylcholine