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

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-␥/IL-4 cytokine production to investigate CD4 ϩ , Th1, and Th2 cells in the peripheral blood of children with untreated, newly diagnosed Crohn's disease (CD) (n ϭ 23) and matched healthy controls (n ϭ 49). Th1 cytokine levels were lower in CD patients compared with controls (p ϭ 0.006) and strongly correlated with levels of albumin and hematocrit (r ϭ 0.51, p ϭ 0.007 and r ϭ 0.35, p ϭ 0.052, respectively). An age-dependent increase in Th1 cells was observed (p Ͻ 0.0005); however, no correlation was found between age, clinical end points, %CD4ϩ , 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 diseaserelated 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. (Pediatr Res 63: 257-262, 2008)

Cytokine Profiles in Peripheral Blood of Children and Adults With Crohn Disease

“…This supports our previous observation as well as other published data in treatment-naïve pediatric CD patients. 24, 26 These results, however, are in contrast to findings from other studies that have evaluated the Th1/Th2 profiles in the intestinal mucosa and/or peripheral blood associated with CD. In adults, increased expression of IFN-γ was found in peripheral blood or intestinal tissue of adult CD patients compared with controls, in line with the accepted dogma of a Th1-mediated mechanism of disease.…”

“…In our previous study, newly diagnosed pediatric CD patients also possessed lower IFN-γ compared with healthy controls but the IL-4 did not differ significantly between the two groups. 24 In the present study, IL-6 percentages did not differ between the two pediatric groups. No differences in IFN-γ, IL-4, and IL-6 percentages were found between adult CD patients and controls.…”

“…24 In the current pilot study, we aimed to validate this finding and to expand the spectrum of cytokines and age of CD patients and controls to include adults. The intracellular production of IFN-γ, TNF-α, IL-4, and IL-6, cytokines that have been associated with various auto-inflammatory conditions including IBD, were analyzed in whole blood by flow cytometry.…”

Few differences in cytokines between patients newly diagnosed with type 1 diabetes and their healthy siblings

“…Newborn children have a low production of IFN-c and an increase in IFN-c production is thought to be related to the maturation of the immune system [32]. Studies have found a decrease in intracellular levels of cytokines or a decline in T and B cells with age [33,34]. The shift from Th2 to Th1 is not supported by an increase of IFNc with age in this study.…”

Vanillin Improves and Prevents Trinitrobenzene Sulfonic Acid-Induced Colitis in Mice

“…T-helper cells are a subgroup of lymphocytes that activate and direct other immune cells through release of cytokines. An imbalance between Th1 and Th2 cytokines has been implicated in the pathogenesis of IBD, particularly CD (Holland et al, 2008). Moreover, an increase in proinflammatory cytokines, mainly Th1 cytokines, is observed in patients with CD, also suggesting that CD is a Th1-mediated disease (Neurath et al, 1997).…”