Chronic inhibition of cyclooxygenase-2 attenuates antibody responses against vaccinia infection.
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.
Bernard
Matthew P
MP
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Bancos
Simona
S
Chapman
Timothy J
TJ
Ryan
Elizabeth P
EP
Treanor
John J
JJ
Rose
Robert C
RC
Topham
David J
DJ
Phipps
Richard P
RP
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D056724:Immunity, Humoral / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014615:Vaccinia / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*
D000914:Antibodies, Viral; D052246:Cyclooxygenase 2 Inhibitors; D007074:Immunoglobulin G; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2