title: Histamine 1 Receptor Blockade Enhances Eosinophil-Mediated Clearance of Adult Filarial Worms.
abstract: Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis and river blindness. The goal of this study was to characterize the role of histamine during Litomosoides sigmodontis infection of BALB/c mice, a murine model of filariasis. Time course studies demonstrated that while expression of histidine decarboxylase mRNA increases throughout 12 weeks of infection, serum levels of histamine exhibit two peaks-one 30 minutes after primary infection and one 8 weeks later. Interestingly, mice treated with fexofenadine, a histamine receptor 1 inhibitor, demonstrated significantly reduced worm burden in infected mice compared to untreated infected controls. Although fexofenadine-treated mice had decreased antigen-specific IgE levels as well as lower splenocyte IL-5 and IFNγ production, they exhibited a greater than fourfold rise in eosinophil numbers at the tissue site where adult L. sigmodontis worms reside. Fexofenadine-mediated clearance of L. sigmodontis worms was dependent on host eosinophils, as fexofenadine did not decrease worm burdens in eosinophil-deficient dblGATA mice. These findings suggest that histamine release induced by tissue invasive helminths may aid parasite survival by diminishing eosinophilic responses. Further, these results raise the possibility that combining H1 receptor inhibitors with current anthelmintics may improve treatment efficacy for filariae and other tissue-invasive helminths.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America; Institute for Medical Microbiology, Immunology, and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Ellen Mueller
authors.initials: EM
authors.lastname: Fox
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Morris
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Hübner
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Maryland, United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: Mitre
mesh_terms: D000818:Animals; D002927:Cimetidine / Q000008:administration & dosage / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D005368:Filariasis / Q000188:drug therapy* / Q000469:parasitology; D005370:Filarioidea; D005786:Gene Expression Regulation; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012744:Sex Ratio; D013154:Spleen / Q000166:cytology; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011969:Receptors, Histamine H1; D007073:Immunoglobulin E; D016593:Terfenadine; D002927:Cimetidine; C093230:fexofenadine