title: Effects of antihistamines on innate immune responses to severe bacterial infection in mice.
abstract: BACKGROUND
  Sedating and non-sedating histamine H(1) receptor (H1R) antagonists and H2R blockers are widely used drugs which are generally considered to be safe medications. However, recently, these drugs have been shown to possibly impair the outcome of perforating appendicitis in children.
  
  
  OBJECTIVE
  It was the aim of this study to characterize the effects of histamine receptor blockade in severe bacterial infections in more detail.
  
  
  METHODS
  To obtain information on the safety of histamine receptor blockade in more detail, we used pharmacological and genetic approaches targeting histamine receptors and performed cecal ligation and puncture (CLP), a mouse model of septic peritonitis. After induction of septic peritonitis, morbidity and mortality were monitored closely.
  
  
  RESULTS
  Here, we show that oral treatment with first-generation H1R antihistamine diphenhydramine, H2R blocker cimetidine and H3/4R blocker thioperamide impairs optimal innate immune responses in severe murine bacterial sepsis. However, these adverse effects are not mediated by H1R, as mice deficient for H1R show similar rates of morbidity and mortality after CLP as their wild-type controls. Similarly, the second-generation antihistamine desloratadine neither affects morbidity nor mortality after CLP.
  
  
  CONCLUSIONS
  Our findings indicate that sedating first-generation H1R antihistamines and H2R blockers might impair innate immune responses to bacteria and that these drugs should be used with caution in patients with severe bacterial infections.
authors.affiliation: Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Metz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Doyle
authors.forename: Carsten
authors.initials: C
authors.lastname: Bindslev-Jensen
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Torsten
authors.initials: T
authors.lastname: Zuberbier
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy / Q000276:immunology; D004155:Diphenhydramine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D054828:Histamine H3 Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D017336:Loratadine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011968:Receptors, Histamine / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D018926:Anti-Allergic Agents; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating; D054828:Histamine H3 Antagonists; D010880:Piperidines; D011968:Receptors, Histamine; D017336:Loratadine; D004155:Diphenhydramine; C121345:desloratadine; C052075:thioperamide