Scientists Raise Red Flag Over Some Painkillers and Immunizations

Scientists Raise Red Flag Over Some Painkillers and Immunizations

April 05, 2005

Over-the-counter painkillers such as nonsteroidal anti-inflammatory drugs like ibuprofen, and the newer Cox-2 selective drugs such as Celebrex or Bextra, may reduce the body’s ability to make antibodies, which are crucial for proper function of the immune system, University of Rochester scientists report in the Journal of Immunology.

Although it is well known that these types of medicines clamp down on inflammation by altering the function of many different types of cells, this is the first time scientists have shown a direct connection between the popular painkillers and B lymphocytes, or white cells known as B cells. The UR group showed that human B cells highly express the Cox-2 enzyme, and that blocking the enzyme activity is what reduces the B cells’ ability to make antibodies.

The Cox-2 connection to B cells has both positive and negative implications for the immune system, according to corresponding author Richard P. Phipps, Ph.D., professor of Environmental Medicine, and Microbiology and Immunology, at the UR Medical Center. Lead author on the paper is graduate student Elizabeth Ryan.

The primary role of B cells is to make the antibodies that lock onto infectious bugs and fight them off. B cells also serve as the immune system’s memory by recognizing and eliminating germs that have previously tried to infect us.

So, for example, when a person is vaccinated the goal is to promote an immune response by making antibodies to protect against a certain illness. But if the vaccinated patient takes a Cox-2 selective inhibitor, or an NSAID such as Advil or aspirin, to ease pain at the injection site, the drug could reduce the amount of antibody produced by the vaccine. In the military, where soldiers receive multiple vaccines, the problem could be greater, Phipps said.

On the other hand, the use of drugs that inhibit the Cox-2 enzyme might be a potential therapy for diseases involving too many abnormal B cells, such as non-Hodgkin’s lymphoma, where the goal is to stop their proliferation, or in autoimmune diseases that are marked by abnormal antibody production, he said.

At this point, Phipps’ group has demonstrated the B-cell connection to Cox-2 in studies of healthy human cell samples, in vitro, and in defective mice that lack the Cox-2 enzyme. But the immune response to vaccines in humans is very complex and can be influenced by many factors, including age, underlying chronic diseases, and type of vaccine given. The next step is to begin clinical trials to study the antibody production in healthy people who receive vaccines.

“Drugs that target the Cox enzymes play an important role in blunting inflammation and fever,” Phipps said. “However, inflammation and fever are normal aspects of the human immune system. Blocking these pathways during initial vaccination or infection may reduce our ability to produce antibodies that protect us.”

Understanding the mechanisms involved in Cox-2 activity is key since the use of Cox-2 inhibitors, both over-the-counter and in prescription form, is so common. Cox-2 is a human enzyme that plays a role in diseases such as arthritis, and other inflammatory ailments.

Recently, questions have been raised about the safety and effectiveness of Cox-2 selective inhibitors. Last year Merck & Co. voluntarily recalled its prescription Cox-2 selective painkiller Vioxx due to increased risks of strokes and heart attacks.

Phipps’ research is funded by the U.S. Public Health Service, Leukemia Society of America, James P. Wilmot Discovery Fund, and the university’s Environmental Health Sciences Center.

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