Scientists at the University of Rochester Medical Center have recently discovered that over-the-counter painkillers in the non-steroidal, anti-inflammatory class, such as ibuprofen and also the more recently developed cyclooxygenase-2 specific inhibitors like Celebrex, Vioxx and Bextra, may affect the immune system by decreasing its ability to make antibodies.

“We have always had an interest in the cyclooxygenase-2 enzyme since it was discovered here at the UR,” Professor of Environmental Science, Microbiology and Immunology Richard Phipps said. “What we discovered was that human B lymphocytes, the ones that make antibodies, when activated, highly express this COX-2 enzyme.”

The COX-2 specific drugs have been some of the most famous drugs in the market over the past few years.

The lead author on the paper is fourth-year graduate student Elizabeth Ryan.

“If you leave the B cells untreated or unactivated, they do not express COX-2,” Ryan said. “And when you activate these cells, there is increased COX-2 expression. However, when you inhibit COX-2 activity, you reduce antibody production by the B cells.”

It has already been known that these painkillers can lead to various side-effects such as gastrointestinal bleeding as well as increased risks of heart attacks and strokes, following long-term usage.

“What happened with Vioxx and Bextra was that they were pulled off the market, because, amongst the many people who had used them for long periods of time of six months or more, some had heart attacks and strokes,” Phipps said.

In experiments where blood drawn from humans was placed in cultures containing various drugs, it was discovered that the cultures containing the COX-2 specific inhibitors produced a smaller amount of antibodies than the controls.

“The cultures that have COX-2 inhibiting enzymes make much less antibodies because they need that enzyme to optimally produce antibodies,” Phipps said. “We also showed that mice that had their COX-2 gene knocked out had much less antibody production than the mice that had this gene intact.”

These findings may have several implications not only in health and medicine, but in implementing health policies as well.

“For example, if you’re vaccinated and are interested in mounting a humoral immune response, then it’s possible that if you take these drugs, you might reduce antibody production,” Ryan said. “These are some of the broad implications of this discovery. However, there are some cases of auto-antibody productions, in which case one would want to reduce antibody production. Thus, these drugs may have therapeutic benefits in some instances.”

Vaccines can actually produce the same response in smaller dosages in the absence of such painkillers and drugs in the person’s immune system.

“What we would like to do next is to develop a few animal models in which we can immunize against either bacteria or viruses, and then evaluate when is it most important to have this enzyme,” Phipps said.

These findings were reported in the Journal of Immunology. The research study was supported by a grant from the National Institute of Health.

Sridharan can be reached at asridharan@campustimes.org.



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