Abstract
The complex interaction between inflammatory mediators in allergic rhinitis (AR) is determined by the role of genetic polymorphisms, including interleukin (IL) and toll-like receptor (TLR) genes. This study aimed to discuss the effects of H1-antihistamines on IL and TLR systems. Several ILs involved in AR pathogenesis are: IL-4 (rs2243250, rs1800925, rs1801275, rs2227284, rs2070874), IL-6 (rs1800795, rs1800797), IL-10 (rs1800871, rs1800872), IL-12R (rs438421), IL-13 (rs1800925, rs20541), IL-17 (rs3819024), IL-18 (rs360721, rs360718, rs360717, rs187238), IL-23R (rs7517847), and IL-27 (rs153109, rs17855750). In the IL system, histamines stimulate the IL production in Type 2 helper T (Th2) cells through protein kinase A (PKA), janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, and the activation of H1-histamine receptor and histidine decarboxylase (HDC) genes. On contrary, antihistamines down-regulate the H1-histamine receptor gene expression through the transcription suppression of HDC and IL genes and suppress histamine basal signaling through the inverse agonistic activity. TLRs involved in AR pathogenesis are TLR2 (rs4696480, rs3804099, rs5743708), TLR4 (rs4986790), TLR6 (rs2381289), TLR7 (rs179008, rs5935438), TRL8 (rs2407992, rs5741883, rs17256081, rs4830805, rs3788935, rs178998), and TLR10 (rs11466651). In the TLR system, histamines trigger the TLR expression by stimulating interferon-γ (IFN-γ) to up-regulate mast cells and by stimulating receptor-interacting protein (RIP) to activate IκB kinase-β. Contrastingly, antihistamines suppress TIR-domain-containing adaptor protein inducing IFN-β (TRIF) and RIP protein and thus inhibit the expression of TLR. In addition, several studies indicated that H1-antihistamines inhibit the IL and TLR systems indirectly.
Highlights
Allergic rhinitis (AR) is one of the most common allergic diseases
Another study conducted by Osna et al [43] analyzed the regulation of IL-10 secretion by histamines. They showed that histamines could stimulate IL-10 production in Th2 cells which is reversed by both H1- and H2- receptor antagonists and by protein kinase A (PKA) inhibitors H8 and rp-adenosine-3’,5’-cyclic monophosphothionate (Rp-cAMPS)
Histamines trigger the production of IL through several mechanisms, including: [1] histamines stimulate the IL production in Th2 cells which is reversed by both H1- and H2- receptor antagonists, PKA inhibitors H8, and Rp-cAMPS [43], [2] histamines stimulate the IL secretion and transcription through PKA and JAK-STAT pathway [45], [3] histamines stimulate the IL production through the transcription activation of the H1-histamine receptor [19] and histidine decarboxylase (HDC) genes [20]
Summary
Allergic rhinitis (AR) is one of the most common allergic diseases. Submitted: 10 November 2015 / Accepted: 3 March 2016. AR has been associated with the main reasons why people visit primary care [1]. AR is not a life-threatening disease, but it can significantly impair the quality of life [2]. Total funding issued to AR was estimated approximately 5.3 billion dollars per year [3]. The incidence of AR in the United States (US) was estimated approximately 40 million cases [4]. Nihlen et al [5] reported that the prevalence of AR was estimated around 15% in men and 14% in women.
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