title: Possible effects of repeated exposure to ibuprofen and acetaminophen on the intestinal immune response in young infants.
abstract: There has been an exponential increase in the frequency of immune deviations in young children. Consequently, research investigating environmental causes for this increase has become a Public Health priority. We have summarized the experimental observations and epidemiological data that could link repeated acetaminophen and ibuprofen exposure in early infancy to this increase. Recent observations on the maturational immunity of the intestinal sub-mucosal lamina propria underscore indeed the importance of prostaglandins (PGE2s). PGE2 appearing at this sub-mucosal level is a product of arachidonic acid metabolism mediated by type-2 cyclooxygenase (COX-2) situated on the membrane of many immune cells. Moreover, it seems that acetaminophen - like ibuprofen - also carries a non-selective inhibitory action on peripheral COXs, besides its central action. This inhibitory action of acetaminophen on COX2 only relates to physiological, low arachidonic acid concentrations. This explains the difference in anti-inflammatory effects. The impact of repeated inhibition of mucosal PGE2 synthesis due to COX-inhibitor exposure on maturational immunity has been demonstrated in animal experiments. Repeatedly exposed young animals do not develop tolerance to food antigens and exhibit autoimmune deviations. Several recent epidemiological studies have also reported on the magnitude of acetaminophen and ibuprofen exposure in children and the increase in immune deviations, it is important to better understand the potential negative impact of repeated inhibitions of prostaglandin synthesis by COX2s during infancy. Since acetaminophen and ibuprofen are commonly administered analgesics and antipyretics, a well-designed prospective strategy for pharmacovigilance and -epidemiology of COX-inhibitor exposure in infancy is urgently needed.
authors.affiliation: Department of Paediatrics and NICU, CHC-Site St Vincent, 4000 Liège-Rocourt, Belgium. Electronic address: jean-paul.langhendries@chc.be.
authors.forename: J-P
authors.initials: JP
authors.lastname: Langhendries
authors.affiliation: Department of Paediatrics and NICU, Gasthuisberg Hospital, KUL, 3000 Leuven, Belgium. Electronic address: karel.allegaert@uzleuven.be.
authors.forename: K
authors.initials: K
authors.lastname: Allegaert
authors.affiliation: Division of Pediatric Clinical Pharmacology, Children's National Medical Center, Washington, USA; Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Paediatric Pharmacology, University Children's Hospital Basel, Switzerland. Electronic address: jvandenanker@cnmc.org.
authors.forename: J N
authors.initials: JN
authors.lastname: Van Den Anker
authors.affiliation: Department of anesthesiology, Cliniques Universitaires St Luc, UCL, 1200 Brussels, Belgium. Electronic address: francis.veyckemans@uclouvain.be.
authors.forename: F
authors.initials: F
authors.lastname: Veyckemans
authors.affiliation: Department of Paediatrics, Cliniques Universitaires St Luc, UCL, 1200 Brussels, Belgium. Electronic address: francoise.smets@uclouvain.be.
authors.forename: F
authors.initials: F
authors.lastname: Smets
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015232:Dinoprostone / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects*; D007108:Immune Tolerance / Q000187:drug effects; D007223:Infant; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D023421:Models, Animal; D018448:Models, Immunological
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D015232:Dinoprostone; D007052:Ibuprofen