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

Pak, Seung*; Holland, Nina*; Garnett, Elizabeth A.; Mileti, Elizabeth; Mahadevan, Uma; Beckert, Rachel; Kanwar, Bittoo; Heyman, Melvin B.

Journal of Pediatric Gastroenterology and Nutrition: June 2012 - Volume 54 - Issue 6 - p 769–775
doi: 10.1097/MPG.0b013e3182455bb3
Original Articles: Gastroenterology

Background: Increasing evidence suggests that cytokine dysregulation in T-helper 1 and T-helper 2 (TH1/TH2) subsets contributes to the pathogenesis of Crohn disease (CD). The present pilot study examines the hypothesis that cytokine profiles differ between pediatric and adult patients with CD.

Methods: Production of TH1 cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) and of TH2 cytokines interleukin-4 (IL-4) and IL-6 was analyzed in peripheral blood of patients with CD and healthy controls (n = 20) using flow cytometry after in vitro stimulation.

Results: In both pediatric and adult subjects, frequencies of TNF-α CD4+ T cells were higher in patients with CD than in controls (P = 0.009 and P = 0.047, respectively). Percentages of cells expressing IL-4 were slightly increased (P = 0.036), whereas those for IFN-γ were decreased (P = 0.009) in pediatric patients with CD compared with controls. As expected, the overall production of TH1 cytokines was higher in adults compared with pediatric subjects. When memory CD4+CD45RO+ T cells were considered, lower IFN-γ expression was observed in pediatric subjects with CD compared with controls (P = 0.009), matching the trend seen in the general CD4+ T cell population. The percentage of CD4+CD45RO+ T cells was increased in adult patients with CD compared with pediatric patients with CD (P = 0.016).

Conclusions: The present study describes a peripheral blood TH1/TH2 cytokine imbalance in CD and suggests different immunological mechanisms in children and adults for disease pathogenesis.

*School of Public Health, University of California, Berkeley

Department of Pediatrics

Department of Medicine, University of California, San Francisco, CA.

Address correspondence and reprint requests to Melvin B. Heyman, MD, MPH, Department of Pediatrics, University of California-San Francisco, 500 Parnassus Ave, MU4East, Box 0136, San Francisco, CA 94143-0136 (e-mail:

Received 6 December, 2010

Accepted 30 November, 2011

Supported by grants from the Packard Foundation, the Crohn's and Colitis Foundation of America, the Children's Digestive Health and Nutrition Foundation/North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Career Development Award (B.K.), and NIH R03 DK063187, K08 DK083334, M01 RR01271, T32 DK007762, K24 DK60617, and PO1 ES009605. This article's contents are solely the responsibility of the authors and do not necessarily represent official views of the Packard Foundation, the Crohn's and Colitis Foundation of America, and the NIH.

The authors report no conflicts of interest.

Copyright 2012 by ESPGHAN and NASPGHAN