In 1922, Homer Swift tested the hypothesis that salicylates may induce an antibody response, termed “immune bodies,” following exposure to live and killed bacterial antigens. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in modulating immune responses was first investigated decades ago. 15 Due to the paucity of clinical trials and studies examining this question, we expanded our review of the literature to cover clinical studies of all age groups, including pediatric and adult populations in addition we reviewed in vivo and in vitro laboratory studies to explore potential mechanisms that could explain blunting of the immune response by antipyretic analgesics. 15 However, their analysis was restricted to children 6 years or less and did not discuss in vitro or laboratory studies. examined the clinical studies that investigated the effect of prophylactic antipyretic analgesics on post-vaccination adverse reactions and antibody response to vaccination. The focus of this review is to evaluate previous work exploring the effects of antipyretic analgesics on the immune responses following vaccination. 13 In a recent policy statement WHO advised against administration of prophylactic oral analgesics due to lack of evidence of effectiveness and/or the potential for affecting vaccine response. 12 The American Academy of Pediatrics in 2010 stated that more studies are needed to explore the clinical impact of antipyretics on vaccination and recommended discussing risks and benefits of prophylactic or therapeutic antipyretics with parents. 11 Despite this, the current CDC Vaccine Information Statement (VIS) for DTaP instructs caregivers to use antipyretics at time of vaccination and for the next 24 hours to reduce fever and pain however, this has not been updated since its publication in 2007. 10 To date, routine administration of antipyretics around the time of vaccination is discouraged by many.
Furthermore, this prompted discontinuation of enrollment in a placebo-controlled randomized trial of acetaminophen given for prevention of post-vaccine fever in infants. This finding resulted in the rejection of the prevailing notion that prophylactic antipyretic use around the time of vaccination is harmless. The primary purpose of the study was to assess the effect of antipyretics in reducing fever and other vaccine related reactogenicity, but the preliminary immunogenicity report showed significantly reduced antibody levels in the prophylaxis group. The same allocation was maintained during the booster “secondary” immunizations. 9 In this study, infants receiving primary immunization were divided into two groups, a prophylaxis group who received acetaminophen and a control group. demonstrated that while acetaminophen (paracetamol) prophylaxis significantly reduced fever following routine childhood immunization, it simultaneously blunted the immune response to several vaccine antigens. 6-8 However, an open label, randomized study by Prymula et al. 1,2 They have been shown to decrease vaccine reactogenicity, 3-5 and until recently have not been associated with decreased vaccine immunogenicity. 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.Īntipyretic analgesics are widely used around the time of vaccination to ameliorate fever and pain. Recent work has focused on the involvement of nuclear and subcellular signaling pathways. The mechanism by which antipyretic analgesics reduce antibody response remains unclear and not fully explained by COX enzyme inhibition. This effect has only been noted following primary vaccination with novel antigens and disappears following booster immunization. Only few randomized clinical trials demonstrated blunted antibody response of unknown clinical significance. Observational studies reporting on antipyretic use around the time of immunization concluded that their use did not affect antibody responses. Our objective was to review literature evaluating the effect of antipyretic analgesics on vaccine immune responses and to highlight potential underlying mechanisms. While antipyretic analgesics are widely used to ameliorate vaccine adverse reactions, their use has been associated with blunted vaccine immune responses.