Chronic inhibition of cyclooxygenase-2 attenuates antibody responses against vaccinia infection

Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Vaccine (Impact Factor: 3.62). 11/2009; 28(5):1363-72. DOI: 10.1016/j.vaccine.2009.11.005
Source: PubMed


Generation of optimal humoral immunity to vaccination is essential to protect against devastating infectious agents such as the variola virus that causes smallpox. Vaccinia virus (VV), employed as a vaccine against smallpox, provides an important model of infection. Herein, we evaluated the importance cyclooxygenase-2 (Cox-2) in immunity to VV using Cox-2 deficient mice and Cox-2 selective inhibitory drugs. The effects of Cox-2 inhibition on antibody responses to live viruses such as vaccinia have not been previously described. Here, we used VV infection in Cox-2 deficient mice and in mice chronically treated with Cox-2 selective inhibitors and show that the frequency of VV-specific B cells was reduced, as well as the production of neutralizing IgG. VV titers were approximately 70 times higher in mice treated with a Cox-2 selective inhibitor. Interestingly, Cox-2 inhibition also reduced the frequency of IFN-gamma producing CD4(+) T helper cells, important for class switching. The significance of these results is that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), and other drugs that inhibit Cox-2 activity or expression, blunt the ability of B cells to produce anti-viral antibodies, thereby making vaccines less effective and possibly increasing susceptibility to viral infection. These new findings support an essential role for Cox-2 in regulating humoral immunity.

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    • "The effect of COX inhibition on antibody production in an infectious scenario has revealed conflicting results. During vaccinia virus infection, deletion of COX-2 resulted in decreased levels of several subclasses of IgG due to failure of immunoglobulin class-switching (Bernard et al., 2010). Similarly, pathogen-specific antibody production was decreased by COX-2 inhibition during Mycobacterium bovis-induced arthritis (Turull and Queralt, 2000). "
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