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.

Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling

“…Eosinophils have prior been defined as an essential effector cell component of the antifilarial immune response against various filarial parasite life cycle stages in vitro and in vivo ( 54 ), including an active involvement in direct mf killing ( 2 , 55 ), in granulocytic content release at the site of infection ( 2 , 4 , 56 ), mf-targeted Ab-dependent cytotoxicity mechanisms ( 55 , 57 ), and granuloma clustering around infective and adult stages ( 10 , 12 , 58 ). Our present study illustrates that whereas a muted eosinophil response is evident in the absence of IL-4/IL-13 signaling, low eosinophilia is still an integral component of immune attrition to juvenile adults in IL-4Rα mice.…”

High‐fat diet promotes prostate cancer growth through histamine signaling

“…Fexofenadine hydrochloride (Fexo, 0.25 g/L for an average dosage of 20 mg/kg/day; TCI, Tokyo, Japan) and ranitidine hydrochloride (Rani, 0.05 g/L for an average dosage of 4 mg/kg/day; Wako, Osaka, Japan) were administered to mice via drinking water from 5 weeks of age. The concentrations were determined based on previous reports 10,11 . The solutions were freshly prepared once per week as they were reported to be stable for over a week only 12,13 .…”

“…The concentrations were determined based on previous reports. 10,11 The solutions were freshly prepared once per week as they were reported to be stable for over a week only. 12,13 previous report.…”

Neglected Tropical Diseases: Treatment of Dermatological Manifestation of Filariasis with Combination Regimen of Albendazole, Ivermectin, and Loratadine: A Case Report from a Suburban Community in Nigeria

“…Studies by Fox et al [15] suggest that there is an elevation of histamine, which is induced by invasive tissue helminthes, that may aid the survival of helminths by decreasing eosinophilic response. Use of H1 receptor antagonist was found to reduce worm burden from increased eosinophilic clearance significantly, which suggests that the use of H1 antihistamines, such as loratadine, may enhance the efficacy of treatment for filaria and other tissue invasive helminthic infestation.…”