Bacterial DNA does not increase serum corticosterone concentration or prevent increases induced by other stimuli

Bacterial DNA containing unmethylated CpG motifs (CpG DNA) and other microb ial molecules such as lipopolysaccharide (LPS) have a broad range of immune stimulatory effects, which may include many shared cell signaling pathways leading to enhanced cytokine production. Some cytokines activate the hypot halamic-pituitary-adrenal (HPA) axis, and their production is downregulated by products of the HPA axis (glucocorticoids). Because such interactions h ave practical implications in the clinical use of CpG DNA, the present stud y was done to examine the effects of CpG DNA and LPS on serum corticosteron e concentrations. In contrast to LPS, administration of CpG DNA (DNA from E scherichia coli) (30-300 mug) alone did not significantly increase serum co rticosterone concentrations 1 or 4 h after administration. Administration o f CpG DNA to mice prior to LPS caused a synergistic increase in serum tumor necrosis factor-alpha (TNF-alpha), indicative of an immune stimulatory eff ect. LPS and TNF-alpha, however, induced similar levels of corticosterone w ith or without concomitant CpG DNA. Increasing doses of LPS caused peak cor ticosterone levels similar to those induced by LPS in combination with CpG DNA. Exogenous TNF-alpha administered in vivo induced comparable concentrat ions of corticosterone with or without CpG DNA. An alternative stressor (re straint) yielded similar levels of corticosterone with or without CpG DNA. These results indicate that CpG DNA does not induce corticosterone release or alter its release by other stimuli, indicating biologically important di fferences in its immune effect compared to those of LPS, and possibly reduc ed toxicity. (C) 2001 Elsevier Science B.V. All rights reserved.