CATANIA, ITALY—An inexpensive drug may relieve allergic rhinitis symptoms with few side effects: In patients with allergic sensitivity, intranasal aerosolized heparin (15,000 U in 4 mL) administered before an allergen challenge significantly reduced both symptom scores 10 minutes later and eosinophil influx one and six hours post-challenge.[1] The results also suggest that endogenous heparin, a highly charged glycosaminoglycan present in mast cells, may play a role in naturally limiting allergic inflammatory responses.

Although better known as an anticoagulant, heparin, when inhaled, can also modulate antigen-induced bronchoconstriction in atopic patients with asthma and prevent exercise-induced asthma.[2,3] Such actions led Carlo Vancheri, MD, PhD, and colleagues at the Institute of Respiratory Disease at University of Catania, Italy, to investigate whether inhaled heparin could attenuate allergic inflammation of the nasal mucosa as well.

When ambient levels of Parietaria judaica antigens in Catania were low, cromolyn sodium, topical and systemic corticosteroids, and antihistamines were withheld from 10 allergic subjects starting two weeks before the experiment. After nasally inhaling 4 mL of nebulized heparin or saline solution, each subject received incremental nebulized doses of P judaica until a composite symptom score of 6 (of a maximum of 9) was obtained. (Scores were based on nasal blockage, sneezing, and/or rhinorrhea and eye irritation.)

Ten, 60, and 360 minutes later, the researchers reassessed symptoms and performed nasal lavage. Lavage samples were evaluated with eosinophil counts as well as concentrations of eosinophil cationic protein (ECP), an effector of inflammatory tissue damage.

Heparin pretreatment significantly decreased symptom scores at 10 minutes (5.5 vs 8.6 after saline pretreatment). After one hour, the heparin-treated group had significantly lower nasal lavage eosinophil counts than did the saline-treated subjects (33.6% vs 52.0%). At six hours, heparin recipients also had significantly lower eosinophil counts (35.5% vs 56.7%) and ECP levels (23.0 vs 36.6 ng/mL).

HEPARIN ATTENUATES INFLAMMATION

“The significant reduction in symptoms at 10 minutes might be related to the ability of heparin to prevent the release of histamine from mast cells,” Dr. Vancheri remarked to RESPIRATORY REVIEWS Heparin may interfere with stimulation of mast cell mediator secretion by blocking internal calcium release. Later on, “heparin may reduce eosinophil recruitment through different mechanisms: [By] preventing mast cell mediator release, heparin could indirectly down-regulate adhesion molecules on endothelial cells ... limiting eosinophil migration into the nasal mucosa,” he explained. Furthermore, the heavily anionic heparin “may inactivate platelet activating factor, a cationic protein with a potent chemotactic activity for human eosinophils” as well as ECP.

PROMISE FOR THERAPY

“Intranasal heparin attenuated the nasal response to an allergic challenge in atopic rhinitic subjects [but] was well tolerated, and no adverse reaction was noted,” Dr. Vancheri pointed out. “More studies are needed to completely explain the mechanisms by which heparin produces its anti-inflammatory activity; [such research] will allow us to optimize [heparin] use ... in allergic diseases, such as rhinitis and asthma.”

—Mimi Zucker, PhD