Feeding information obtained in one criminal case into the profile of another crime often helps to solve the latter. The literature on two different "crimes," namely, acute systemic
inflammation and
arthritis (including
osteoarthritis [OA] and
rheumatoid arthritis [RA] deals largely with the same "gang" of inflammatory mediators, such as
prostaglandin (PG) E2. Early investigations suggested that microsomal
PGE synthase-1 (mPGES-1; a terminal
PGE2-synthesizing
enzyme) plays a pivotal role in bacterial
lipopolysaccharide (LPS)-induced systemic
inflammation, but overlooked the possibility that the same
enzyme could be involved in OA or RA. Later studies showed that mPGES-1 is indeed a key perpetrator in arthritic diseases, a fact that could have been predicted earlier by pooling the new knowledge about mPGES-1 into the profile of arthritic diseases. In this review, we analyze our recent study on the expression of
erythropoietin-producing hepatocellular (
Eph) receptor kinases and their
ligands,
ephrins, in LPS-induced systemic
inflammation. By pooling these results together with literature data into the profile of RA, we conclude that Eph
kinases and
ephrins are prime suspects for being involved in the pathogenesis of RA. We further conjecture that the involvement of Eph
kinases and
ephrins may be realized via the induction of angiogenesis in the inflamed joint, promotion of leukocyte infiltration, and activation of the infiltrated cells. Studies to test this new hypothesis seem warranted, and our prediction is that the "smoking gun" will be found.