Les prostaglandines et l’immunité du chorion sous-muqueux intestinal. Questions à propos de l’usage répété du paracétamol et de l’ibuprofène en bas âge

Abstract

Immune deviations have been shown to exponentially increase in young children. As a consequence, research investigating possible environmental reasons for this increase is considered a public health priority. An improved understanding of the immunity of the intestinal submucosal lamina propria has demonstrated the importance of prostaglandins (PGE2s) on its local development with general immune consequences further on. PGE2s appear at this intestinal submucosal level from the metabolism of arachidonic acid mediated by type-2 cyclooxygenases (COX2s) situated in the membranes of many immune cells. The potential risk of repeated inhibition of PGE2 synthesis at a young age has been demonstrated in experiments with animals systemically exposed to a non-steroidal anti-inflammatory drug (NSAID). The repeatedly exposed animal cannot develop tolerance to food antigens and exhibits autoimmune deviations. Acetaminophen (paracetamol) and ibuprofen are analgesic and antipyretic medications given to children either alone or in combination, most often without medical prescription. Recently, it has been demonstrated that paracetamol, like ibuprofen, also carries, besides its central action, a non-selective inhibitory action on peripheral COXs. However, this inhibitory action only relates to physiological concentrations of arachidonic acid and explains the difference in their respective anti-inflammatory effects. Since recently published data have repeatedly reported an increase of immune deviations associated with paracetamol exposure at a young age, it appears important to better understand the possible negative impact of excessive and repetitive inhibitions of the physiological synthesis of prostaglandins by COX2s in childhood during which all immune mechanisms are built up at the intestinal submucosal level. Therefore, a well-designed prospective strategy for pharmacovigilance of these COX inhibitors repeatedly given during childhood is urgently needed.