title: Reduced intracellular T-helper 1 interferon-gamma in blood of newly diagnosed children with Crohn's disease and age-related changes in Th1/Th2 cytokine profiles.
abstract: Abnormal cytokine production by T-helper 1 (Th1)/T-helper 2 (Th2) lymphocytes has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined Th1/Th2 cytokine status in pediatric IBD patients, and results have been inconsistent. We used flow cytometric detection of intracellular IFN-gamma/IL-4 cytokine production to investigate CD4+, Th1, and Th2 cells in the peripheral blood of children with untreated, newly diagnosed Crohn's disease (CD) (n = 23) and matched healthy controls (n = 49). Th1 cytokine levels were lower in CD patients compared with controls (p = 0.006) and strongly correlated with levels of albumin and hematocrit (r = 0.51, p = 0.007 and r = 0.35, p = 0.052, respectively). An age-dependent increase in Th1 cells was observed (p < 0.0005); however, no correlation was found between age, clinical end points, %CD4+, or Th2 cell numbers. In conclusion, the Th1 cytokine levels in blood are lower in early onset CD patients than in healthy children and are directly associated with disease-related clinical parameters. In future studies of pediatric IBD patients, it will be critical to consider the effect of age and disease progression on cytokine status in intestinal mucosa and peripheral blood.
authors.affiliation: School of Public Health, University of California, San Francisco, California 94143, USA. ninah@berkeley.edu
authors.forename: Nina
authors.initials: N
authors.lastname: Holland
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garnett
authors.forename: Nishat
authors.initials: N
authors.lastname: Shaikh
authors.forename: Karen
authors.initials: K
authors.lastname: Huen
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: Anthony
authors.initials: A
authors.lastname: Olive
authors.forename: Harland S
authors.initials: HS
authors.lastname: Winter
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Gold
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Cohen
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Kirschner
authors.forename: Melvin B
authors.initials: MB
authors.lastname: Heyman
mesh_terms: D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D000375:Aging / Q000276:immunology*; D001799:Blood Sedimentation; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D016207:Cytokines / Q000097:blood*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006400:Hematocrit; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000097:blood*; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D011446:Prospective Studies; D012709:Serum Albumin / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014481:United States / Q000453:epidemiology
chemical_list: D016207:Cytokines; C508598:IL4 protein, human; D012709:Serum Albumin; D015847:Interleukin-4; D007371:Interferon-gamma