Effects of chromium and copper depletion on lymphocyte reactivity to mitogens in diabetes-prone BHE/cdb rats.

Objective: The purpose of this study was to measure effects of chromium (Cr) and copper (Cu) depletion on lymphocyte reactivity to mitogens in diabetes-prone BHE/cdb rats.

Methods: A 2 x 2 factorial research design was used, and 40 BHE/cdb rats were fed with Cr- and/or Cu-depleted diets or adequate Cr and/or Cu diets for 21 wk. Cr and Cu concentrations in diets and mineral concentrations of tissues of BHE/cdb rats were measured by using flame and graphite furnace atomic absorption spectrometry. Three glucose tolerance tests were performed to monitor the development of diabetes or glucose intolerance at weeks 12, 18, and 21. Splenocytes (2 x 10(6)) were incubated with phytohemagglutinin-l (PHA-L), concanavalin A (ConA), and lipopolysaccharides (LPSs), respectively, for 72 h. Four hours before the end of the incubation, splenocytes were pulsed with 3H-thymidine. The 3H-thymidine uptake by lymphocytes was used to calculate a stimulation index.

Results: According to glucose tolerance tests, these rats did not develop diabetes or impaired glucose tolerance throughout the study. Average Cr concentrations were 0.98 to 1.03 mg Cr/kg of diet in adequate Cr diets and 8.2 to 14 micrograms Cr/kg of diet in Cr-depletion diets. Average Cu concentrations were 3.6 to 6.4 mg Cu/kg of diet in adequate Cu diets and 1.1 to 1.3 mg Cu/kg of diet in Cu-depletion diets. Organ weights did not differ significantly among treatment groups at the end of the study. Cr or Cu depletion significantly affected iron, zinc, and magnesium concentrations in the liver. A significant interactive effect of Cr and Cu was observed on lymphocyte proliferation with PHA-L stimulation at 25 micrograms/mL (P < 0.006). However, there were no significant effects of dietary treatment on lymphocyte proliferation with 10 micrograms/mL of PHA-L, ConA, or LPS stimulations.

Conclusions: When Cr and Cu were adequate in the diets, there was an enhanced effect of Cu or Cr on lymphocyte proliferation. However, when Cr was depleted in the diet, there was a suppressive effect of Cu on lymphocyte proliferation. This result indicates that adequate amounts of Cr and Cu in the diet support the immune system.