Effect of antipyretic analgesics on immune responses to vaccination

Abstract

While antipyretic analgesics are widely used to ameliorate vaccine adverse reactions, their use has been associated with blunted vaccine immune responses. Our objective was to review literature evaluating the effect of antipyretic analgesics on vaccine immune responses and to highlight potential underlying mechanisms. Observational studies reporting on antipyretic use around the time of immunization concluded that their use did not affect antibody responses. Only few randomized clinical trials demonstrated blunted antibody response of unknown clinical significance. This effect has only been noted following primary vaccination with novel antigens and disappears following booster immunization. The mechanism by which antipyretic analgesics reduce antibody response remains unclear and not fully explained by COX enzyme inhibition. Recent work has focused on the involvement of nuclear and subcellular signaling pathways. More detailed immunological investigations and a systems biology approach are needed to precisely define the impact and mechanism of antipyretic effects on vaccine immune responses.

Keywords: NSAIDs; antibody responses; antipyretic analgesics; immune responses; prophylaxis; vaccination.

Figure 1.

Antipyretics analgesics inhibition of post-vaccination immune response. This figure illustrates the different mechanisms by which antipyretic analgesics might inhibit post-vaccine adaptive immune response as suggested by the referenced studies. Vaccine antigen delivered at injection site induces immune and inflammatory mediators which triggers leukocyte migration and activates dendritic cells (DC) [upper left]. DCs capture, process and present antigen to naive CD4 T cells and induce their proliferation and differentiation into T-helper cells (Th0). Th0 influenced by cytokines and other stimuli differentiate into T-helper subsets Th1 (associated with cellular responses) and Th2 (associated with humoral responses). Th2 cells interact with B cell and secrete cytokines (IL4, IL5, IL13) leading to B cell proliferation and differentiation into antibody-secreting plasma cells and memory B cells. Insert: Major intracellular signaling pathways that lead to activation of nuclear factors and expression of cellular end products. PKC: Protein Kinase C; NF-kB: Nuclear factor κ B; NFAT: Nuclear factor of activated T-cells; ERK: extracellular signal regulated kinases; JNK: Jun N terminal kinase; MAPK: mitogen-activated protein kinase; ATF2: Activating transcription factor-2; Cox-2: Cyclo-oxygenase 2; Bcl-XL: B lymphocyte; BLIMP-1:B lymphocyte induced maturation protein-1; XBP-I: X-box-binding protein1.