Published online 11 January 2008 | Nature | doi:10.1038/news.2008.436


Do antihistamines make allergies worse?

Medicated mice react more to bee stings than non-medicated mates.

Stung by medication: antihistamines make mice react more violently to bee venom.GETTY

Taking antihistamines can be a great way to fight off an allergic attack. But new research suggests it also might also make the next attack come on stronger.

Allergies are immune reactions to foreign substances that normally pose no threat to the body, from peanuts to pollen, that can set in after repeated exposure. In theory, even if someone has a genetic predisposition to react to peanuts, they should not react to the first peanut they encounter: it’s the second one that they need worry about.

Antihistamines, with their ability to disrupt the immune response that leads to annoying reactions like runny noses and swelling tissues, have long been considered the ideal way to control allergies. But their long-term effects on the immune system are unknown.

To explore this, a team led by Pål Johansen at the University of Zurich, Switzerland studied 50 mice that were initially injected with bee venom, a substance that nearly all organisms develop an allergy to upon exposure. Half of the mice were also given 100 micrograms of the antihistamine Clemastine just before they were given venom and 100 micrograms on each of the two days afterwards.

Six weeks later Johansen and his team injected the mice with another dosage of bee venom and monitored the allergic reactions. They report in Clinical and Experimental Allergy1 that mice given antihistamines reacted more violently to the second venom injection.

Going up, going down

“We believe that the antihistamines were doing more than disrupting the immediate immune reaction to the first venom dosage,” says Johansen. “We think they were also keeping the immune system from getting used to that dosage.” That means the mice on allergy medication had no chance to build up a tolerance to the allergen.

In a second part of the study, Johansen’s team desensitized the mice to the bee venom using immunotherapy — a process of introducing tiny amounts of an allergenic substance to an allergic individual, slowly helping the immune system to tolerate the substance (in this case they used one-third of the bee venom dose used to provoke a reaction). Unlike antihistamines, immunotherapy can permanently change the way the body responds to a substance and cure allergies.

Mice that had originally been on antihistamines when sensitized with venom responded more poorly to the immunotherapy than the other mice. “This was really surprising because others2,3 have claimed that antihistamines would aid the process of immunotherapy, and that is simply not what we saw,” says Johansen.

Rodent test

Such work is important for understanding how the immune system interacts with antihistamines, says Roger Katz, an allergist at the University of California School of Medicine, Los Angeles. But, he adds, “there is a problem of mice and men”.

Human immunotherapy is typically done over the course of months or years, not weeks, says Katz. And the mice in this study were given a lot of Clemastine for their weight. If they happen to metabolize the antihistamine more slowly than people, this could lead to drug accumulation, which could affect immune system function and potentially explain the study results, says Katz.


But there is no evidence that rodents and people metabolize Clemastine at different rates, says Cezmi Akdis, director of the Swiss Institute of Allergy and Asthma Research in Davos, Switzerland. Antihistamines were originally tested on rodents before being used on humans, he adds, and there have been decades of research on medication in these animals.

Only two studies suggest antihistamines help immunotherapy, and this is the first to contradict them, says Akdis. “We definitely need more research in this area,” he says. 

  • References

    1. Johansen, P. et al. Clin. Exp. Allergy DOI 10.1111/j.1365-2222.2007.02904.x (2008)
    2. Ohashi, Y., Nakai, Y. & Murata, K. Ann. Allergy Asthma Immunol. 96, 600-605 (2006) | PubMed |
    3. Müller, U., Hari, Y. & Berchtold, E. J. Allergy Clin. Immunol. 107, 81-86 (2001) | Article | PubMed |
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