title: Chronic inhibition of cyclooxygenase-2 attenuates antibody responses against vaccinia infection.
abstract: 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.
authors: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors: Matthew P
authors: MP
authors: Bernard
authors: Simona
authors: S
authors: Bancos
authors: Timothy J
authors: TJ
authors: Chapman
authors: Elizabeth P
authors: EP
authors: Ryan
authors: John J
authors: JJ
authors: Treanor
authors: Robert C
authors: RC
authors: Rose
authors: David J
authors: DJ
authors: Topham
authors: Richard P
authors: RP
authors: Phipps
mesh_terms: 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*
chemical_list: D000914:Antibodies, Viral; D052246:Cyclooxygenase 2 Inhibitors; D007074:Immunoglobulin G; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2