Friday, October 16, 2009

A Few Inflammatory Remarks



# 3841



Today in the British Medical Journal, The Lancet, we get a study that suggests that giving babies acetaminophen (Tylenol) right before or immediately after getting a vaccination may inhibit or lower their immune response.


A mild fever is a common response to many vaccinations, and is a normal part of the inflammatory response.  Some parents, on the advice of their pediatricians, have routinely given acetaminophen to their children to avoid this reaction.


This report in the mainstream press from the AP.   A hat tip to Treyfish on FluTrackers for putting me on the scent of this story.


Giving babies Tylenol may blunt vaccine effects

Finding knocks common advice for parents looking to curb fever after shots

updated 6:30 p.m. ET, Thurs., Oct . 15, 2009


Giving babies Tylenol to prevent fever when they get childhood vaccinations may backfire and make the shots a little less effective, surprising new research suggests.


It is the first major study to tie reduced immunity to the use of fever-lowering medicines. Although the effect was small and the vast majority of kids still got enough protection from vaccines, the results make "a compelling case" against routinely giving Tylenol right after vaccination, say doctors from the U.S. Centers for Disease Control and Prevention.


(Continue . . . )


The study’s summary is available online. Below are a few excerpts, but follow the link to read the whole thing. Note that paracetamol is the UK name for Tylenol.



Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials



Although fever is part of the normal inflammatory process after immunisation, prophylactic antipyretic drugs are sometimes recommended to allay concerns of high fever and febrile convulsion. We assessed the effect of prophylactic administration of paracetamol at vaccination on infant febrile reaction rates and vaccine responses.



Although febrile reactions significantly decreased, prophylactic administration of antipyretic drugs at the time of vaccination should not be routinely recommended since antibody responses to several vaccine antigens were reduced.



This isn’t the first indication that certain types of medications can interfere with a vaccine’s effectiveness.   A study several years ago indicated that NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) could lower the body’s antibody response.


Tylenol, while an antipyretic, is not an NSAID, which makes the above study all the more interesting.


Although the full impact of adults taking NSAIDs on the immune response from vaccination isn’t known, I confess that I avoided taking NSAIDs for a couple of days after I got my flu shot last month, simply out of an abundance of caution. 


This isn’t a medical recommendation, it is simply what I did. You should always discuss any medical decisions with your personal medical care provider.



The study which prompted my decision, appeared in The Journal of Immunology, 2006, 177: 7811-7819, is:


Cyclooxygenase-2 Inhibition Attenuates Antibody Responses against Human Papillomavirus-Like Particles

Elizabeth P. Ryan*, Christine M. Malboeuf, Matthew Bernard, Robert C. Rose, and Richard P. Phipps  

Vaccination to generate protective humoral immunity against infectious disease is becoming increasingly important due to emerging strains of virus, poorly immunogenic vaccines, and the threat of bioterrorism.


We demonstrate that cyclooxygenase-2 (Cox-2) is crucial for optimal Ab responses to a model vaccine, human papillomavirus type 16 virus-like particles (HPV 16 VLPs). Cox-2-deficient mice produce 70% less IgG, 50% fewer Ab-secreting cells, and 10-fold less neutralizing Ab to HPV 16 VLP vaccination compared with wild-type mice.


The reduction in Ab production by Cox-2–/– mice was partially due to a decrease in class switching. SC-58125, a structural analog of the Cox-2-selective inhibitor Celebrex reduced by 70% human memory B cell differentiation to HPV 16 VLP IgG-secreting cells.


The widespread use of nonsteroidal anti-inflammatory drugs and Cox-2-selective inhibitory drugs may therefore reduce vaccine efficacy, especially when vaccines are poorly immunogenic or the target population is poorly responsive to immunization.


A little less complex is this summary which appeared in April of 2005 on the University of Rochester Medical Center’s website.



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.

(Continue . . . )


And again from the University of Rochester, we get a more recent study which seems to reaffirm earlier suspicions.


Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells

Simona Bancosa, Matthew P. Bernarda, David J. Tophamb and Richard P. Phippsa 


Available online 5 April 2009.


The widely used non-steroidal anti-inflammatory drugs (NSAIDs) function mainly through inhibition of cyclooxygenases 1 and 2 (Cox-1 and Cox-2). Unlike Cox-1, Cox-2 is considered an inducible and pro-inflammatory enzyme.


We previously reported that Cox-2 is upregulated in activated human B lymphocytes and using Cox-2 selective inhibitors that Cox-2 is required for optimal antibody synthesis. It is not known whether commonly used non-prescription and non-Cox-2 selective drugs also influence antibody synthesis. Herein, we tested a variety of Cox-1/Cox-2 non-selective NSAIDs, namely ibuprofen, tylenol, aspirin and naproxen and report that they blunt IgM and IgG synthesis in stimulated human peripheral blood mononuclear cells (PBMC).


Ibuprofen had its most profound effects in inhibiting human PBMCs and purified B lymphocyte IgM and IgG synthesis when administered in the first few days after activation. As shown by viability assays, ibuprofen did not kill B cells.


The implications of this research are that the use of widely available NSAIDs after infection or vaccination may lower host defense. This may be especially true for the elderly who respond poorly to vaccines and heavily use NSAIDs.



One of the problems with vaccines, and with any medicine for that matter, is that other drugs we take and sometimes even the foods we eat, can interfere with (or exacerbate) their effects.


We know the immune response to vaccines can vary widely from one person to the next.  While there are likely many factors at work (including individual differences in our immune systems), the co-administration of other medicines can’t be ignored.


More research is obviously needed, but knowing about some of these interactions now can allow us to make better choices in the interim.  

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