Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 128, Issue 6, Pages 1286-1294Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2011.06.023
Keywords
Antihistamine; bacterial infections; immune suppression; innate immunity; cytokines; signal transduction; sepsis
Categories
Funding
- Swiss National Science Foundation [31003A-122221]
- Swiss National Science Foundation (SNF) [31003A-122221] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
Background: Antihistamines are considered safe and used worldwide against allergy, pruritus, nausea, and cough and as sleeping aids. Nonetheless, a growing number of reports suggest that antihistamines also have immunoregulatory functions. Objective: We examined the extent and by what potential mechanisms histamine-1-receptor (H1R) antagonists exert immune suppressive effects. Methods: Immune suppression by antihistamines and immunosuppressants was tested in mice infected with Listeria monocytogenes. Potential modes of action were studied in vitro by using murine and human cells. We also tested whether injection of clemastine in healthy volunteers affected the activation of peripheral macrophages and monocytes. Finally, therapeutic application of clemastine-mediated immune suppression was tested in a murine model of sepsis. Results: Clemastine and desloratadine strongly reduced innate responses to Listeria monocytogenes in mice as did dexamethasone. The immune suppression was MyD88 independent and characterized by inhibition of the mitogen-activated protein kinase-extracellular signal-regulated kinase signaling pathway, leading to overall impaired innate immunity with reduced TNF-alpha and IL-6 production. Surprisingly, the observed effects were H1R independent as demonstrated in H1R-deficient mice. Moreover, in a double-blind placebo-controlled clinical trial, 1 intravenous administration of clemastine reduced the TNF-alpha secretion potential of peripheral blood macrophages and monocytes. This inhibition could be exploited to treat sepsis in mice. Conclusions: The safety profile of antihistamines may need to be revisited. However, antihistamine-mediated immune suppression may also be exploited and find applications in the treatment of inflammatory diseases. (J Allergy Clin Immunol 2011;128:1286-94.)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available