Testing and typing of eicosanoid-patterns

Abstract

Eicosanoids are pleiotrope mediators with essential function in most biological processes. The network of inter- and intracellular signalling requires coordinated cellular information processing. The cross-talk is characterised by complex non-linear responses to combinations of different stimuli and cells, but little is known about the density of these interactions. Here I have analysed eicosanoid interactions carried out by functional eicosanoid testing and typing (FET) in leucocytes from healthy subjects and patients suffering from inflammatory diseases. The known eicosanoid pattern scoring was extended to metabolically linked prostaglandin E(2) and peptido-leukotrienes pathways, both alone and in all pair wise combinations, for basal, maximal synthesis capacity, acetylsalicylic acid, and neuropeptide modification. Eicosanoids fluctuated over twenty minutes context-dependent dynamically, demanding further data integration. The integration suggested that many stimuli converge for quantitative discrimination applying a total eicosanoid pattern score (TEP). Varying cellular activities affect FET and thereby TEP. The non-additive metabolic interactions were consistent with known mechanisms of metabolic pathway cross-talk. FET-based modelling of eicosanoid circuits most suitably reflects the fundamental impact of eicosanoids in maintaining cellular integrity of organ and body function. This might improve our present understanding of complex cellular eicosanoid interactions of inflammatory diseases and might be applied for diagnostic considerations.