BML-111, a lipoxin receptor agonist, modulates the immune response and reduces the severity of collagen-induced arthritis.
OBJECTIVE
Lipoxins (LXs) are endogenous antiinflammatory and pro-resolving eicosanoids generated during various inflammatory conditions. Recent research has revealed the novel immunomodulatory function of LXs. The aim of this study is to investigate whether LXs modulate the pathogenesis of collagen-induced arthritis (CIA), a typical chronic immune-mediated inflammatory disease.


RESULTS
CIA was induced in DBA/1 mice and BML-111, a lipoxin A4 receptor agonist, was administrated. Results indicated that compared with untreated CIA mice, both clinical disease activity scores and histological destruction of joint were significantly reduced in BML-111-treated CIA mice. The dampened joint injury was accompanied by decreased concentrations of serum pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 in BML-111-treated CIA mice. In addition, proliferation of isolated spleen cells, as well as circulating levels of antibody to type II collagen, were reduced significantly in BML-111-treated CIA mice.


CONCLUSIONS
BML-111 attenuated CIA in part by negatively regulating the immune response, which implicates the potential pharmacological value of LXs in the treatment of chronic immune-mediated inflammatory diseases such as RA.
Zhang
L
L
Department of Pathophysiology, Chongqing Medical University, Chongqing, 400016, PR China.
Zhang
X
X
Wu
P
P
Li
H
H
Jin
S
S
Zhou
X
X
Li
Y
Y
Ye
D
D
Chen
B
B
Wan
J
J
D000818:Animals; D000843:Ankle Joint / Q000187:drug effects; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology* / Q000503:physiopathology*; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D007109:Immunity / Q000502:physiology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007213:Indomethacin / Q000031:analogs & derivatives / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D044045:Lipoxins / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009025:Morpholines / Q000494:pharmacology; D044042:Receptors, Formyl Peptide / Q000819:agonists* / Q000502:physiology*; D012720:Severity of Illness Index; D013154:Spleen / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D024043:Collagen Type II; C469988:Fpr1 protein, mouse; D007074:Immunoglobulin G; D015850:Interleukin-6; D044045:Lipoxins; D009025:Morpholines; D044042:Receptors, Formyl Peptide; D014409:Tumor Necrosis Factor-alpha; C471852:indomethacin morpholinylamide; D007213:Indomethacin