Enhanced metabolism of arachidonic acid by macrophages from nonobese diabetic (NOD) mice

The inbred nonobese diabetic (NOD) mouse spontaneously develops an autoimmune diabetes, which is now recognized as an experimental model for human type I insulin-dependent diabetes mellitus (IDDM). The autoimmune reaction, specifically directed against pancreatic beta cells (insulitis), involves both macrophages and T lymphocytes. The study of the production of cyclooxygenase and lipoxygenase derivatives of arachidonic acid metabolism shows that in some conditions, and in particular in the presence of zymosan A, macrophages from NOD mice produced significantly more 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and leukotriene C4 (LTC4) than macrophages from age- and sex-matched C57BL/6 mice. Moreover, zymosan A-stimulated macrophages from NOD females produced significantly more LTC4 than did macrophages from NOD males. These results may be of interest, given the bidirectional relationship between the various cytokines involved in the destruction of beta cells of the islets of Langerhans and different eicosanoids.