Azelastine is more potent than olopatadine n inhibiting interleukin-6 and tryptase release from human umbilical cord blood-derived cultured mast cells.
BACKGROUND
Mast cells are involved in early- and late-phase reactions by releasing vasoactive molecules, proteases, and cytokines. Certain histamine-1 receptor antagonists and other antiallergic drugs seem to inhibit the release of mediators from rat and human mast cells.


OBJECTIVE
Azelastine and olopatadine are antiallergic agents present in the ophthalmic solutions azelastine hydrochloride (Optivar, Asta Medica/Muro Pharmaceuticals, Tewksbury, MA), and olopatadine hydrochloride (Patanol, Alcon Laboratories, Fort Worth, TX), respectively. We investigated the effect of these drugs on interleukin-6 (IL-6), tryptase, and histamine release from cultured human mast cells (CHMCs).


METHODS
CHMCs were grown from human umbilical cord blood-derived CD34+ cells in the presence of stem cell factor and IL-6 for 14 to 16 weeks. Sensitized CHMCs were pretreated with various concentrations of azelastine or olopatadine for 5 minutes. CHMCs were then challenged with anti-immunoglobulin E, and the released mediators were quantitated.


RESULTS
The greatest inhibition of mediator release was seen with 24 microM azelastine; this level of inhibition was matched with the use of 133 microM olopatadine. At this concentration, these drugs inhibited IL-6 release by 83% and 74%, tryptase release by 55% and 79%, and histamine release by 41% and 45%, respectively. Activated CHMCs were characterized by numerous filopodia that were inhibited by both drugs as shown by electron microscopy.


CONCLUSIONS
These results indicate that azelastine and olopatadine can inhibit CHMCs activation and release of IL-6, tryptase, and histamine. On an equimolar basis, azelastine was a more potent inhibitor than olopatadine.
Kempuraj
Duraisamy
D
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts 02111, USA.
Huang
Man
M
Kandere
Kristiana
K
Boucher
William
W
Letourneau
Richard
R
Jeudy
Sheila
S
Fitzgerald
Kim
K
Spear
Kathleen
K
Athanasiou
Achilles
A
Theoharides
Theoharis C
TC
D018926:Anti-Allergic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003990:Dibenzoxepins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D000069605:Olopatadine Hydrochloride; D010793:Phthalazines / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D053802:Tryptases
D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D015850:Interleukin-6; D010793:Phthalazines; D000069605:Olopatadine Hydrochloride; D012697:Serine Endopeptidases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases; C020976:azelastine