Parenteral zinc supplementation in adult humans during the acute phase response increases the febrile response

The acute phase response (APR) that follows injury or infection is characterized by a decrease in serum zinc concentrations, which we hypothesized benefits the host. Additionally, we proposed that preventing this decline by supplementing zinc would result in an exaggerated APR as indicated by elevated temperatures, increased serum cytokine concentrations, interleukin 6 and the acute phase protein (ceruloplasmin). A prospective, randomized, double-blinded, clinical trial was conducted. Patients on home parenteral nutrition with a diagnosis of catheter sepsis and patients with a diagnosis of pancreatitis, also on total parenteral nutrition (TPN), were recruited for the study. Following enrollment, block randomization was used to assign patients to receive 0 mg (n = 23) or 30 mg (n = 21) of zinc per day for the first 3 d of TPN. Blood samples for measurement of serum zinc, copper, ceruloplasmin and interleukin-6 were obtained upon enrollment and bn d 1 through 3 of TPN. The highest temperatures reported on these days in the medical record were also recorded. Repeated measures ANOVA was used to determine differences in the primary outcome variables over time. No significant differences between groups were observed in serum interleukin-6 or ceruloplasmin concentrations. A significantly higher (P = 0.035) temperature was observed in the zinc-supplemented group compared with the control group on d 3 of parenteral nutrition. We conclude that parenteral zinc supplementation in patients experiencing a mild APR resulted in an exaggerated APR as evidenced by a significantly higher febrile response.