Adequacy of mucosal biopsies for evaluation of intestinal cytokine-specific mRNA

Abstract

Endoscopic biopsies are being increasingly utilized to investigate cytokine profiles in normal and diseased intestine. To evaluate the adequacy of mucosal biopsies as a source of cytokine-specific mRNA, we measured their content of interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2) mRNA by reverse transcription-polymerase chain reaction and compared it to that of autologous lamina propria mononuclear cells in control and inflammatory bowel disease-involved specimens. High-quality total RNA was recovered more consistently from cell isolates than from biopsies. Interleukin-1 beta mRNA was reliably detected in both cell and biopsy samples, whereas IL-2 mRNA was measurable in all lamina propria cells but not always in biopsies. Compared to controls, levels of IL-1 beta were significantly elevated in Crohn's disease and ulcerative colitis cells and biopsies, and a weak but significant correlation existed between values derived from the two sources. In contrast, only ulcerative colitis cell isolates but not biopsies contained significantly reduced concentrations of IL-2 mRNA compared to those of control and Crohn's disease samples, and no correlation was found between cell and biopsy contents. Widely different levels of cytokine-specific mRNA were present in closely adjacent biopsies, particularly for IL-2. These results suggest that mucosal biopsies are suitable to assess some but not all cytokine-specific mRNA due to variation in RNA recovery, intrinsic level of cytokine gene expression, and substantial variability of cytokine transcripts.