Evaluation of the efficacy of antihistamines using human monocyte-derived dendritic cells stimulated with histamine.
BACKGROUND
It has been reported that histamine induces CD86 expression and chemokine production in human immature monocyte-derived dendritic cells (MoDCs), which can be blocked by both H(1)- and H(2)-receptor antagonists.


OBJECTIVE
We sought to examine whether the efficacy of H(1)-type antihistamines can be assessed by using MoDCs.


METHODS
We examined the suppressive effects of 1 H(2)-type antihistamine (cimetidine) and 5 different H(1)-type antihistamines (cetirizine, diphenhydramine, ketotifen, olopatadine, and emedastine) on the induction of CD86 and IL-8 production by MoDCs from 23 healthy individuals stimulated with histamine. We also examined the responses of MoDCs from 13 patients with chronic urticaria to these antihistamines, and compared the in vitro efficacy with the actual clinical response to antihistamines evaluated by patient and physician assessments.


RESULTS
All the antihistamines we examined suppressed the increase of CD86(+) cells after histamine stimulation in a dose-dependent fashion, and all H(1)-type antihistamines were more efficacious than cimetidine. IL-8 production stimulated with histamine was also suppressed by cetirizine, ketotifen, and olopatadine. Unexpectedly, the suppressive effect of these antihistamines on the CD86 augmentation was highly variable among different healthy control participants. Interestingly, in 10 of 13 cases of chronic urticaria, this in vitro analysis of antihistamines correlated with the clinical response to antihistamines.


CONCLUSIONS
This study suggests that the evaluation of antihistamines using MoDCs can be a useful method for the screening of effective antihistamines, for the comparison of the efficacy of antihistamines, and for predicting the efficacy of antihistamines on an individual basis.
Ohtani
Tomoyuki
T
Department of Dermatology, Tohoku Unviersity Graduate School of Medicine, Sendai, Japan. aiba@mail.cc.tohoku.ac.jp
Aiba
Setsuya
S
Mizuashi
Masato
M
Kawamoto
Yuji
Y
Tagami
Hachiro
H
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism*; D051940:B7-2 Antigen; D017332:Cetirizine / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D002927:Cimetidine / Q000494:pharmacology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006632:Histamine / Q000494:pharmacology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology / Q000627:therapeutic use; D006635:Histamine H2 Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D014581:Urticaria / Q000188:drug therapy
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D039563:Histamine H1 Antagonists, Non-Sedating; D006635:Histamine H2 Antagonists; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D002927:Cimetidine; D006632:Histamine; D017332:Cetirizine