ANALYSIS OF INTERLEUKIN-4 AND INTERLEUKIN-10 AND THEIR ASSOCIATION WITH THE LYMPHOCYTIC INFILTRATE IN THE SMALL-INTESTINE OF PATIENTS WITH CELIAC-DISEASE

Background-Concentrations of proinflammatory cytokines are raised in t he small intestine of patients with coeliac disease after ingestion of gluten but there are equivalent data an interleukin-4 (IL-4) and inte rleukin-10 (IL-10) producing cells, These cytokines are known to exert important regulatory effects on proinflammatory cytokine production f rom lymphocytes and macrophages. Aims-To investigate whether there Is a primary deficiency of IL-4 and IL-10 producing cells and their site of production in the small intestine of patients with coeliac disease in relation to the changes in inflammatory cell infiltrate. Patients-J ejunal biopsy specimens from patients with coeliac disease (11 untreat ed, 10 treated) and nine disease controls were studied. Methods-Immuno histochemical staining of sections for IL-4 and IL-10 cytokines and th e cell phenotypic markers CD3 (T lymphocytes) and CD45 (total inflamma tory cell infiltrate) was carried out using monoclonal antibodies, Exp ression of IL-4 and IL-10 messenger RNA was detected by in situ hybrid isation with oligonucleotide probe cocktails for each cytokine, Result s-IL-4 and IL-10 mRNA and protein were detected in the lamina propria of treated and untreated coeliac patients and disease controls but not in the epithelium. A significant increase in the number of CD45 (p<0 . 005) and CD3 (p<0 . 05) positive cells was found in the lamina propr ia of patients with untreated coeliac disease compared with treated co eliac patients and disease controls but there were no differences in I L-4 or IL-10 between these groups with either method. Conclusions-Ther e is no primary deficiency of IL-4 and IL-10 producing cells in the sm all intestine of patients with coeliac disease, Detectable concentrati ons Georgetown of IL-4 and IL-10 were found in control University, pat ients which suggests that these cytokines are involved in normal mucos al immunoregulation. The increased number of T lymphocytes but not. IL -4 or IL-10 producing cells in the lamina propria of patients with unt reated than in those with treated disease suggests not only that the l amina propria is the major mucosal compartment for cytokine production but that newly recruited mucosal T lymphocytes are directed to a pred ominant Th1 and not a Th2 cytokine response in coeliac patients on a d iet containing gluten.