Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Δημήτριος Ρηγόπουλος, Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
Νικόλαος Καβαντζάς, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Πάντος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δημήτριος Στραβοπόδης, Αναπληρωτής Καθηγητής, Τμήμα Βιολογίας, ΕΚΠΑ
Παρασκευή Ξεπαπαδάκη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Δημήτριος Τραφαλής, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιορδάνης Μουρούζης, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μοριακοί και κυτταρικοί ανοσολογικοί μηχανισμοί κατά τις αντιδράσεις υπερευαισθησίας στα μη στεροειδή αντιφλεγμονώδη φάρμακα: ex vivo διερεύνηση στο ανθρώπινο περιφερικό αίμα
Translated title:
Molecular and cellular immunological mechanisms in hypersensitivity reactions to Non Steroidal Anti-inflammatory Drugs: ex vivo investigation in human peripheral blood
Summary:
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequent causes of drug hypersensitivity reactions (DHRs), yet the underlying mechanisms remain poorly understood. Although histamine plays an key role in allergic reactions, its contribution to the etiological pathogenesis of DHRs is unknown. The aim of this study was to investigate the association of circulating histamine with the development of DHRs induced by NSAIDs.
This working hypothesis was methodologically approached by the fluorometric determination of basal histamine levels in whole peripheral blood and plasma of 16 patients with reported DHRs to one or more NSAIDs and/or paracetamol. Eighteen healthy volunteers, as well as 13 cancer patients who had developed DHRs to platinum derivatives and were undergoing desensitisation enrolled as control groups.
Whole blood histamine levels did not significantly differ between patients and healthy subjects. Basal plasma histamine levels in the patients with DHRs to a single NSAID were significantly higher than the respective values determined in healthy subjects (P < 0.001). In contrast, comparable differences were not observed (P > 0.2) in patients with DHRs to multiple NSAIDs. In addition, plasma histamine levels in patients reporting DHRs to cyclooxygenase (COX) -1 selective inhibitors were significantly higher compared to the respective values obtained in patients with DHRs to COX-2 selective inhibitors (P < 0.05). Moreover, basal plasma histamine levels in cancer patients were higher than those determined in healthy subjects (P < 0.05), but comparable to those of the patients with DHRs to NSAIDs (P > 0.1). Furthermore, they were significantly elevated following desensitization, and particularly in women (P < 0.05) and in patients with no metastases (P <0.05), in those who did not manifest a DHR during desensitisation (P < 0.05) and in patients who had not been treated with platinum derivatives in the past (P < 0.05). In the latter subgroup, histamine plasma levels were correlated with the chemotherapy cycle in which the reaction occurred (P < 0.01).
In conclusion, basal histamine levels in the plasma of patients who had previously developed DHRs were higher than the corresponding levels observed in healthy subjects who had not developped DHRs. The results provided preliminary evidence for the contribution of circulating histamine to the differential manifestations of DHRs to NSAIDs. The data provide the lead for the prospective in-depth investigation of the factors that influence and/or determine the putative regulatory actions of histamine in the etiopathogenesis of hypersensitivity reactions.
Main subject category:
Health Sciences
Keywords:
Cyclooxygenase inhibitors, Drug Hypersensitivity Reactions, Histamine, Human peripheral blood, Non-Steroidal Anti-inflammatory Drugs, Immunopharmacology
Number of references:
308
