Thursday, May 23, 2013

Leukotriene B4 as a possible target in Rheumatoid Arthritis



2006 saw some promising results concerning leukotriene B4 (LTB4)in inflammatory arthritis. M. Chen and colleagues reported on mice studies. Leukotrienes recruit leukocytes to the synovium. As leukotriene B4 is required for inflammatory arthritis, they concluded, that it might be a target for new therapies. Iain B. McInnes had published a viewpoint on “Leukotrienes, mast cells, and T cells” in 2003; link: http://arthritis-research.com/content/5/6/288. “However, it is currently unclear whether LTB4 occupies a sufficiently critical hierarchical position in effector mediator pathways to provide a therapeutic target, given the multiplicity of other chemokines present in synovial tissues to which synovial T cells and indeed other leukocyte subsets are responsive. Thus, although LTB4 antagonism has proved to be of some clinical utility in pulmonary inflammation, it has yet to be properly tested in chronic human synovitis.”

What happened since Iain McInnes published this viewpoint? I’ve found a review by S. Mathis and colleagues, published in 2007: “Role of leukotriene B4 receptors in rheumatoid arthritis”; link: http://www.ncbi.nlm.nih.gov/pubmed/17967719. The authors concluded: “Many recent studies in mouse models have suggested a critical role for LTB(4) and its receptors in the development of inflammatory arthritis. […] suggesting several promising targets for RA in this pathway.” S.P. Mathis and colleagues also published a paper in 2010: “Nonredundant roles for leukotriene B4 receptors BLT1 and BLT2 in inflammatory arthritis”. Cyclooxygenase and lipoxygenase pathways are mediators of inflammation, but if we compare the quantity being processed, COX is the more important of the two pathways. But they concluded: “Thus, BLT2, a unique receptor for 5-lipoxygenase- and cyclooxygenase-1-derived lipid mediators, represents a novel target for therapies directed at treating inflammation associated with arthritis.” Link: http://www.ncbi.nlm.nih.gov/pubmed/20656922.

Recently B. Yousefi and colleagues published: “The role of leukotrienes in immunopathogenesis of rheumatoid arthritis”; link: http://www.ncbi.nlm.nih.gov/pubmed/23529572. Nothing new coming out of this study.

So this is where we stand. LTB4 is a mediator of inflammation and through recruitment of leukocytes might effect arthritis, but we are still not seeing a new therapeutic option in rheumatoid arthritis. Maybe the current rainy weather makes me pessimistic about this approach.

01.09.2016:

S.P. Mathis and colleagues published a paper on more rodent studies. They can prove that BLT2 (a low-affinity leukotriene B(4) receptor) plays a role in arthritis, but “biochemical activities and physiological roles remain unknown”. They concluded: “… BLT2, a unique receptor for 5-lipoxygenase- and cyclooxygenase-1-derived lipid mediators, represents a novel target for therapies directed at treating inflammation associated with arthritis.”
I'm still pessimistic (and today the sun is shining!).
 




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