The metabolic role of zinc in the acute phase response.

Abstract

The acute phase response (APR) that follows injury or infection is characterized by a decrease in serum zinc concentrations. We hypothesized this decline would benefit the host. In addition, 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 (IL-6) and the acute phase protein, ceruloplasmin. A prospective, randomized, double blinded, placebo controlled clinical trial was conducted to investigate the impact of zinc supplementation on a mild APR. Patients on home parenteral nutrition with a diagnosis of catheter sepsis, and patients with a diagnosis of pancreatitis, also on 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 in the first 3 days of TPN therapy. Blood samples for serum zinc, copper, ceruloplasmin and IL-6 were obtained upon enrollment and on days 1 through 3 of TPN. The highest temperatures reported daily in the medical record, on these days, were also recorded. Twenty-four hour urine collections for concentrations of zinc were obtained on days 1 through 3 of TPN to assess for effective supplementation. There were no significant differences between study groups in the patient's sex, age, disease status, weight and baseline concentrations of serum IL-6, zinc or ceruloplasmin. Repeated measure ANOVA was used to determine differences in the primary outcome variables over time. Effective supplementation of zinc was confirmed by significantly higher serum and urine zinc concentrations in the zinc supplemented group (p = 0.0004). There were no significant differences observed in serum IL-6 and ceruloplasmin concentrations between study groups. A significantly higher (p = 0.035) temperature was observed in the zinc supplemented group compared to the control group on day 3 of TPN. We also found a significant correlation (p = 0.0002) between temperature and IL-6 (r = 0.56) in both study groups. We concluded parenteral zinc supplementation in patients experiencing a mild APR results in a significantly higher febrile response.