Critical role of endogenous histamine in promoting end-organ tissue injury in sepsis

Abstract

BackgroundHistamine assumes an important role as a major mediator in various pathologic disorders associated with inflammation and immune reactions. However, the involvement of histamine in the pathological conditions and symptoms of sepsis remains entirely unknown. In this study, we establish that histamine is identified as a contributory mediator to promoting the development of organ injury in sepsis.MethodsHistidine decarboxylase (HDC) gene knockout (HDC−/−) mice, histamine H1-/H2-receptor gene-double knockout (H1R−/−/H2R−/−) mice, and their littermate wild-type (WT) C57BL/6J mice underwent cecal ligation and puncture (CLP) or sham operation. Some WT mice were injected intraperitoneally with d-chlorpheniramine and famotidine 60 min before CLP to block H1- and H2-receptors, respectively.ResultsIn mice rendered septic by CLP, tissue histamine levels were elevated in association with increased HDC expression. Sepsis-induced abnormal cytokine production and multiple organ injury (lung, liver, and kidney) were significantly less pronounced in HDC−/− mice as compared with WT controls, and HDC deficiency had improved survival in sepsis. This benefit corresponded with a significant reduction in activation levels of the nuclear factor (NF)-κB signaling pathway. H1R−/−/H2R−/− mice apparently behaved similar to HDC knockout mice in reducing sepsis-related pathological changes. Pharmacological interventions with H1- and H2-receptor antagonists indicated that both H1- and H2-receptors were involved in septic lung and liver injury, whereas only H2-receptors contributed to septic kidney injury.ConclusionsIn the setting of sepsis, histamine, through activation of H1- and H2-receptors, serves as an aggravating mediator to contribute to the development of sepsis-driven major end-organ failure.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-016-0109-y) contains supplementary material, which is available to authorized users.

Role of G protein‐coupled receptor kinase 2 in oxidative and nitrosative stress‐related neurohistopathological changes in a mouse model of sepsis‐associated encephalopathy

“…; Hattori et al . ). Prior to surgery, mice were identified by tail coloring and were randomly split into the groups using an online tool (https://www.graphpad.com/quickcalcs/).…”

LDK378 inhibits the recruitment of myeloid‐derived suppressor cells to spleen via the p38–GRK2–CCR2 pathway in mice with sepsis

“…The degree of tissue damage was estimated through a light microscope (OLYMPUS BX53, Tokyo, Japan). All slices were evaluated blindly based on the histopathological injuries and scored using a semiquantitative scoring system from 0 to 4 (none, light, moderate, severe and very severe) for the following categories: inflammatory cell infiltration, pulmonary edema, disorganization of parenchyma and hemorrhage as described previously . A total lung injury score was calculated by adding the score of four categories.…”

Perbandingan Angka Kejadian Batuk Pascabronkoskopi pada Kelompok Premedikasi Kombinasi Kodein 10 mg dan Klorfeniramin Maleat 4 mg dengan Premedikasi Tunggal Kodein 10 mg

“…Selain di dalam sel mast, ada juga histamin yang berasal dari beberapa jaringan lain seperti otak yang berfungsi sebagai neurotransmiter serta dalam enterochromaffin like cell (ECL) di lambung. 13,16,17 Salah satu efek histamin adalah muncul efek yang mirip dengan reaksi anafilaktik. Efek histamin lainnya adalah pruritus, edema, nyeri, vasodilatasi, bronkokonstriksi, peningkatan permeabilitas pembuluh darah, serta stimulasi reseptor batuk di saluran napas.…”

“…Kerusakan mukosa saluran napas akan mengakibatkan dilepaskan histamin sehingga terjadi edema di saluran pernapasan, peningkatan produksi sekret saluran napas, serta bronkokonstriksi yang dapat memicu batuk. 10,16 Klorfeniramin 18,19 Penelitian lain juga menunjukkan efektivitas CTM sebagai antitusif baik pada batuk yang disebabkan oleh alergi maupun akibat iritasi saluran napas. Dalam penatalaksanaan batuk pasien dewasa, Asian Conference on Clinical Pharmacy telah merekomendasikan penggunaan antihistamin generasi yang pertama sebagai kombinasi terapi batuk.…”