Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats.
Antihistamines are effective for treatment of seasonal nasal allergy. Recently, prophylactic treatment with antihistamines in patients with pollinosis was reported to be more effective when started before the pollen season. The administration with antihistamines from 2 to 6 weeks before onset of the pollen season is recommended for management of allergic rhinitis in Japan. To determine the reason for the effectiveness of prophylactic treatment with antihistamines, the effects of repeated pre-treatment with antihistamines before provocation with toluene 2,4-diisocyanate (TDI) on their nasal allergy-like behavior and up-regulations of histamine H(1) receptors (H1R) and interleukin (IL)-4 mRNAs in their nasal mucosa were examined. Provocation with TDI induced sneezing and up-regulations of H1R and IL-4 mRNAs in the nasal mucosa of TDI-sensitized rats. Repeated pre-treatments with antihistamines including epinastine, olopatadine, or d-chlorpheniramine for 1 to 5 weeks before provocation with TDI suppressed TDI-induced sneezing and the up-regulations of H1R and IL-4 mRNAs in the nasal mucosa more than their administrations once or for 3 days before TDI provocation. Our data indicate that repeated pre-treatment with antihistamines before provocation with TDI is more effective than their single treatment in reducing nasal allergy-like behavior by causing additional suppression of up-regulations of H1R and IL-4 mRNAs in the nasal mucosa.
Mizuguchi
Hiroyuki
H
Department of Molecular Pharmacology, Institute of Health-Biosciences, The University of Tokushima Graduate School, Japan.
Hatano
Masaya
M
Matsushita
Chiyo
C
Umehara
Hayato
H
Kuroda
Wakana
W
Kitamura
Yoshiyuki
Y
Takeda
Noriaki
N
Fukui
Hiroyuki
H
D000818:Animals; D002744:Chlorpheniramine / Q000008:administration & dosage / Q000494:pharmacology; D003984:Dibenzazepines / Q000008:administration & dosage / Q000494:pharmacology; D003990:Dibenzoxepins / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D000069605:Olopatadine Hydrochloride; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012912:Sneezing / Q000187:drug effects; D013997:Time Factors; D014051:Toluene 2,4-Diisocyanate; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects*
D003984:Dibenzazepines; D003990:Dibenzoxepins; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D014051:Toluene 2,4-Diisocyanate; D015847:Interleukin-4; D000069605:Olopatadine Hydrochloride; D002744:Chlorpheniramine; C053090:epinastine