No abstract

Systemic lupus erythematosus (SLE) is the classical immune-complex disease. Involvement of vital organs, particularly the kidneys and brain, accounts for significant morbidity and mortality. A number of imaging tools are currently available for evaluation of inflammatory conditions. By targeting the increased glucose uptake of infiltrating granulocytes and tissue macrophages, positron emission tomography with fluorine-18 fluorodeoxyglucose ([(18) F]FDG PET/CT) has been shown to delineate inflammation with high sensitivity. Because activated lymphocytes have increased glucose metabolism, [(18) F]FDG PET has been successfully used to visualize large concentrations of these cells in lymphoid organs where antigen presentation and lymphocyte activation occur. Widespread increased FDG uptake in lymph nodes of patients with active SLE, as well as increased thymic uptake, has been described. The most prevalent and dramatic PET/CT finding in neuropsychiatric SLE (NP-SLE) patients is parieto-occipital hypometabolism. In conclusion, PET/CT has become an excellent ancillary tool to assess disease activity and prognosis in SLE patients.

One of the pathways of metabolism of leukotriene B4 (LTB4) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) in leukocytes is oxidation of the 12-hydroxyl group, followed by reduction of the 10,11-double bond. In the case of 12R-HETE and 12S-HETE, this results in the formation of 12-oxo-ETE, 10,11-dihydro-12-oxo-ETE, and the 12R and 12S isomers of 10,11-dihydro-12-HETE (i.e., 12R-HETrE and 12S-HETrE). We investigated the effects of metabolites of 12-HETE formed by this pathway on cytosolic calcium levels and chemotaxis in human neutrophils. Of the above series of metabolites, 12S-HETrE (which has the same absolute stereochemistry at C-12 as 12R-HETE) was the most potent in stimulating both cytosolic calcium levels and chemotaxis. It was slightly less potent than 12R-HETE, consistent with the concept that reduction of the 10,11-double bond results in a loss of biological activity on neutrophils. The effect of 12S-HETrE on calcium levels was blocked by preincubation of these cells with LTB4, suggesting that it acted by stimulating the LTB4 receptor. 12R-HETrE was about 20 times less potent than its 12S isomer in stimulating cytosolic calcium in neutrophils and was also less active as a chemotactic agent. Oxidation of the 12-hydroxyl group to an oxo group resulted in a further loss of biological activity. 12-Oxo-ETE, 8-trans-12-oxo-ETE, and 12-oxo-ETrE had only modest effects on cytosolic calcium levels at concentrations as high as 10 microM and did not display detectable chemotactic activity. However, 12-oxo-ETE and its 8-trans isomer inhibited calcium responses to LTB4 by about 40%. It is concluded that reduction of the 10,11-double bond of 12-HETE results in a slight loss of biological activity on neutrophils, whereas oxidation of the 12-hydroxyl group results in a considerably greater loss of activity.