Non-steroidal anti-inflammatory drugs reduce optimal antibody production in response to vaccination and vaccinia virus infection (45.18)

Abstract

Protective humoral immune responses generated by vaccination, depends on optimal production of antibodies. Non-steroidal anti-inflammatory drugs (NSAIDs) are used to curb undesirable effects of vaccination such as fever. We previously demonstrated that B cells express the “proinflammatory” enzyme cyclooxygenase-2 (Cox-2) in response to activation stimuli such as the TLR9 ligand CpG DNA. Using genetic approaches and small molecule Cox-2 selective inhibitors, we demonstrated that Cox-2 is crucial for optimal antibody production. Expression of plasma cell transcriptional regulatory factors, including Blimp-1 and Xbp-1, were dependent on Cox-2 activity. Significantly fewer antibody secreting plasma cell precursors were generated in the presence of Cox-2 inhibitors, indicating that Cox-2 is essential for human B cell terminal differentiation. Mice chronically treated with Cox-2 inhibitors produced less neutralizing IgG following live virus infection with vaccinia virus. In vitro studies using human B cells show that all commonly used NSAIDs, as well as Tylenol (acetaminophen), at pharmacologic doses, blunt antibody production. Interestingly, a recent clinical trial showed that Tylenol use in infants blunted antibody responses to a variety of vaccines. These new data support the concept that the Cox pathway is necessary for optimal antibody production. The use of NSAIDs, may impair antibody production to vaccination and to certain infections.