The effect of H1 receptor antagonists on peripheral blood mononuclear cells, adenoid cells and primary cell lines.
This study describes the in vitro effect of three H1 receptor antagonists (dexchlorpheniramine, terfenadine and loratadine) on human peripheral blood mononuclear cells (PBMC, n = 30) from allergic patients and healthy individuals. The three H1 receptor antagonists significantly inhibited antigen/mitogen-induced PBMC proliferation in a concentration-dependent manner. Allergen-specific T-cell responses in allergic individuals were similarly inhibited. The effect of the three drugs was also tested in cultures of mononuclear cells derived from adenoid tissue. The growth kinetics were investigated using spontaneously proliferating cell lines to examine whether the inhibition was caused by general toxicity. Three cell lines, HCT 8 (an ileocaecal adenocarcinoma) RPMI 8866 (B-cell line) and 166 A2 (T hybridoma) were tested. Loratadine (< 0.03 microM) and dexchlorpheniramine (< 0.62 microM) altered the kinetics of HCT 8 and RPMI 8866, respectively. When testing RPMI 8866 and 166 A2, the growth-inhibitory effect of terfenadine and loratadine could be neutralized by addition of cell culture filtrate from RPMI 8866 or 166 A2. These culture filtrates are rich in soluble low-affinity IgE receptor (sCD23) and IgE-binding factor (IgEBF), respectively. Our findings show that the antihistamines investigated display some non-convential in vitro anti-allergic properties possibly not related to their interaction with the H1 receptor. In addition, our results suggest: a) The H1 receptor antagonists used differ in their pattern of cell inhibition; b) The inhibitory effect is completely reversible at low drug concentrations.
Holen
E
E
Institute of Clinical Biology, University Hospital, Bergen, Norway.
Elsayed
S
S
Nyfors
A
A
D000234:Adenoids / Q000166:cytology*; D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002744:Chlorpheniramine / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects*; D017336:Loratadine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016593:Terfenadine / Q000494:pharmacology
D006634:Histamine H1 Antagonists; C018904:dexchlorpheniramine; D002744:Chlorpheniramine; D017336:Loratadine; D016593:Terfenadine