Cyclooxygenase Inhibitors Decrease Antibody Response to Vaccination

The effectiveness of vaccination may be significantly diminished if the individual receiving the vaccine has been treated with an inhibitor of cyclooxygenase-1 (COX-1), which also causes a drop in the production of interleukin-17 (IL-17).

The COX enzymes are known modulators of innate immune cell function; however, their contributions to adaptive immunity (antibody production) are relatively unknown. Therefore, investigators at the University of Missouri (Columbia, USA) studied the roles of COX-1 and COX-2 in the humoral immune response to infection with the Lyme disease pathogen Borrelia burgdorferi.

The investigators reported in the November 1, 2009, issue of The Journal of Immunology that in vitro, mouse B cells expressed COX-1 at a constant rate, but upregulated expression of COX-1 and COX-2 as well as their products PGE2, PGF2-alpha, and thromboxane B2, and their receptors following stimulation with B. burgdorferi. In vitro inhibition of COX-1 and/or COX-2 resulted in decreased eicosanoid production and altered antibody production. Importantly, infection of mice lacking COX-1, but not COX-2, activity resulted in a defect in immunoglobulin class switching and a lack of Borrelia-specific IgG production. This defect correlated with decreased IL-6 and IL-17 production, and it could be partially recovered by restoration of IL-6, but fully recovered by IL-17.

Furthermore, sera from COX-1 inhibitor-treated mice were dramatically less effective in killing B. burgdorferi, but borreliacidal activity was restored in COX-1 inhibitor-treated mice administered IL-17. Thus, IL-17 plays a role in antibody production and immunoglobulin class switching in response to infection, and that COX-1 is a critical, previously unrecognized regulator of this response.

"If you are taking aspirin regularly, which many people do for cardiovascular treatment, or acetaminophen for pain and fever and get a flu shot, there is a good chance that you will not have a good antibody response,” said senior author Dr. Charles Brown, associate professor of veterinary pathobiology at the University of Missouri. "These drugs block the enzyme COX-1, which works in tissues throughout the body. We have found that if you block COX-1, you might be decreasing the amount of antibodies your body is producing, and you need high amounts of antibodies to be protected.”

"So far, we have tested this on an animal model and have found that these nonsteroidal drugs do inhibit vaccines, but the next step is to test it on humans,” said Dr. Brown. "If our results show that COX-1 inhibitors affect vaccines, the takeaway might be to not take drugs, such as aspirin, acetaminophen, and ibuprofen for a couple weeks before and after you get a vaccine.”

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