Gastrointestinal (GI) disease is a common manifestation of
HIV infection. Symptoms may result from the acquisition of intestinal
infection, but in certain cases functional and mucosal abnormality may result from mucosal
HIV infection. The pathogenesis of
HIV enteropathy is poorly understood, but a range of neuroenteric disturbances has been described including a reduction in mucosal
substance P (SP).
Inflammatory bowel disease (IBD) is a generic term used to describe two major clinical entities;
Crohn's disease (CD) and
ulcerative colitis (UC). Dysregulation of mucosal
neuropeptide expression has been implicated in the pathogenesis of CD and UC. Mucosal SP expression has been variously described as increased, normal or reduced in intestinal tissue from patients with IBD. In contrast, uniform increases in mucosal SP receptor (SPR) have been described in patients with IBD using quantitative autoradiography. The purpose of this study was to characterize intestinal mucosal SPR
mRNA expression in control, HIV and IBD patients using semiquantitative reverse transcription PCR. Intestinal tissue was obtained during diagnostic colonoscopy from 7 control, 9 HIV-infected and 28 (12 CD and 16 UC) IBD patients.
RNA was isolated from the tissue biopsies, reverse transcribed and amplified with primers specific for SPR. SPR
mRNA expression was detected in 7/7 (100%) of control, 2/9 (22%) of HIV-infected, 12/12 (100%) of CD and 11/16 (69%) of UC intestinal biopsies. These data demonstrate that SPR
mRNA expression is significantly reduced in patients with
HIV infection. Reduced mucosal SPR expression may contribute to the mucosal abnormality, altered intestinal motility and GI symptoms associated with
HIV infection.