Selective Th2 pattern of cytokine secretion in Mycobacterium avium subsp. paratuberculosis infected Crohn's disease.
OBJECTIVE
The pathogenesis of Crohn's disease (CD) remains unclear. A major controversy has been whether infection with Mycobacterium avium subspecies paratuberculosis (MAP) plays a significant role. Current support for a role of MAP is largely based on epidemiological data. The aim of this study was to determine whether MAP detection in gut biopsies is associated with a different cytokine secretion profile as observed in whole blood culture.


METHODS
A whole blood culture system was employed to measure cytokine secretion, using an ELISA assay, in subjects with CD (n = 46), ulcerative colitis (n = 30), irritable bowel syndrome (n = 22) and normal controls (n = 18). MAP status was defined by nested PCR using an IS900 sequence unique to MAP.


RESULTS
Significantly higher levels of interleukin (IL)-4 (P < 0.05) and IL-2 (P < 0.05) were found in MAP+ CD compared to MAP- CD. This was selective, as MAP+ subjects in both normal and disease controls had similar levels of IL-4 and IL-2 to those with no detectable MAP. IL-4 secretion was correlated with IL-2 production in blood cultures in CD (P < 0.01), consistent with a skewed Th2 immune response.


CONCLUSIONS
This data set provides the first evidence of altered T cell function linked to MAP infection in CD, and provides a link between detection of MAP and disease. The pattern of cytokine shift in CD is consistent with the concept that the increasing incidence of CD is in part related to the hygiene theory.
Ren
Zhigang
Z
Discipline of Immunology and Microbiology, School of Biomedical Sciences, University of Newcastle, Newcastle, New South Wales, Australia.
Turton
Jacqueline
J
Borody
Tom
T
Pang
Gerald
G
Clancy
Robert
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000097:blood / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology; D010283:Paratuberculosis / Q000150:complications*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism*
D000942:Antigens, Bacterial; D016207:Cytokines; D007376:Interleukin-2; D015847:Interleukin-4