EFFECT OF PROBIOTICS ON TH1 and TH2 CYTOKINES: RELEVANCE TO PATHOGENESIS and TREATMENT OF ULCERATIVE COLITIS

Abstract

Ulcerative colitis (UC) mucosa is associated with a cytokine imbalance with predominance of Th2 cytokines vs. Th1. A probiotic cocktail maintains remission in patients with pouchitis (Gionchetti, 2000). In addition, probiotics have similar efficacy to mesasal in maintaining remission in UC (Rembacken, 1999). This efficacy may be due to the ability of these organisms to modulate the immune response of the host. Mice fed Lactobacillus casei produce higher levels of the Th1 cytokines, IFNγ and IL‐2, and lower levels of the Th‐2 cytokines, IL‐4, IL‐5 and IL‐6 (Matsuzaki, 2000). Hypothesis Probiotocs may work in UC/pouchitis by up‐regulation of Th1 vs. Th2 cytokines to so restore immunological balance. Study design Five healthy, 5 UC, 5 CD subjects; not on immunosuppression. Trial two different probiotics (Lactobacillus paracasei LAFTI ™L26, and Bifidobacterium lactis LAFTI ™B94) sequentially and randomly with 2 weeks washout. Draw blood at time 0, 2 weeks post probiotic, 4 weeks (2 weeks post washout) and 6 weeks (2 weeks post second probiotic) for PBMC. Measure by ELISA cytokines in stimulated and unstimulated 44 h cultures. Stimulate PBMC with B94, L26, or other bacterial antigens. Results There are preliminary Th1 (TNFα, IFNγ) and Th2 (IL‐4, IL‐10) data for feeding B94, but TNFa data only for L26, for n = 2 healthy subjects. Baseline (0 week), for TNFa, unstimulated was 371 pg/mL and stimulated was for gram positive (gm+) antigens 2166 pg/mL and for gram negative (gm–) antigens 1022 pg/mL. For IFNγ, baseline stimulated and unstimulated levels were negligible. For IL‐4, baseline levels in unstimulated and stimulated cultures were low (< 100 pg/mL). With B94 (2 weeks), TNFα increased in both unstimulated (923 pg/mL) and stimulated PBMC, 4588 pg/mL (gm+), 3040 pg/mL (gm–), and significant IFNg was detected in gm+ stimulated cultures (> 1000 pg/mL), but not in unstimulated or gm– stimulated cultures. IL‐4 was down‐regulated to undetectable levels. Levels of IL‐10 varied. With L26 (week 6) there were increased levels of TNFα in unstimulated cultures (517 pg/mL) but decreased levels in stimulated cultures, 1751 pg/mL (gm +), 940 pg/mL (gm–). Conclusion The preliminary data for B94 but not L26 support the hypothesis that probiotics may prevent relapse of UC or pouchitis by effecting up‐regulation of Th1 vs. Th2 cytokines. The Gionchetti probiotic cocktail that was used to prevent pouchitis, contained both bifidobacteria and lactobacilli. It is not known which probiotic effected that treatment, but these preliminary data indicate probiotic effects on the immune system, which are diverse.

Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects

“…Although the PBMCs assay used in the present study was widely used for testing probiotic immunomodulatory properties (Cayzer et al 2001;O'Mahony et al 2006;Pochard et al 2002), the results of such in vitro studies have rarely been linked to in vivo effects.…”

Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis

“…Th1 cells predominantly secrete IL-2 and IFN-c, and involve in the cellular immune response, inflammation and acute rejection, whereas Th2 cells primarily secrete IL-4 and IL-5 and contribute to the humoral immune response. 18,19 According to this study, Th1 cells dominate the UC model. After treatment with FMT, Th2 cells become dominant, and the Th1/Th2 balance tends toward the control group.…”