Th1 Subset
The Th1 cell pathway supports cell-mediated immunity, preventing disease from intracellular pathogens like viruses, certain bacteria, yeast, fungi and protozoans. Th1 cellassociated immunity also has a major role in preventing tumor cell development. However, if naïve T cells are chronically Th1 polarized, an overactive cell-mediated immune response can result. For example, persistently high secretion of IL-12 will cause Th1 cells to produce large amounts of pro-inflammatory cytokines like IFN-γ and TNF-α. These cytokines further activate macrophages to produce additional pro-inflammatory mediators (i.e. IL- 12 and IL-18) in a positive feedback loop that has potential pathological consequences (see figure 1).
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Persistent Th1-mediated inflammation of the gastrointestinal tract is associated with pathologies like Crohn’s disease,3 H. pylori gastritis, cellular autoimmunity, chronic recurrent inflammation and possibly rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. This Th1 rigidity and the potential pathological consequences can be moderated by upregulating the production of Th2 dominant cytokines, like IL- 4, IL-10 and IL-13. These cytokines inhibit the development of Th1 cells and macrophage activation and, therefore, can prevent inflammatory tissue damage resulting from an overabundance of Th1 cell stimulation.(8) Furthermore, the immunosuppressive cytokines IL-10 and TGF-β, released by regulatory T cells, also down-regulate Th1 rigidity and help control colitis and other inflammatory diseases.(9) Certain probiotic strains can help down-regulate these Th1 dominant disorders and return balance to the immune response. For example, TNF-α plays a key role in the pathogenesis of intestinal inflammation in Crohn’s disease, a disease associated with Th1 polarization. Borruel et al. (2002) studied the effect of probiotic bacteria on TNF-α production by obtaining ileal specimens from ten patients with Crohn’s disease. They observed a significant reduction in the production of TNF-α by inflamed Crohn’s disease mucosa when cultured with L. casei or L. bulgaricus, but not with L. crispatus or E. coli.(10) The authors concluded that these probiotic strains had the ability to attenuate the release of the pro-inflammatory cytokines that promote Th1 rigidity by interacting with the intestinal mucosal immunocompetent cells.
Furthermore, in mouse studies it was found that a probiotic mixture of nine different bacterial strains ameliorated recurrent Th1-mediated murine colitis by inducing IL-10 secretion and promoting development of IL-10 dependent TGF-β bearing regulatory cells. Daily administration of 2 mg (approximately 3 billion bacteria) of this probiotic mixture for three weeks to mice during a remission period induced an immunoregulatory response involving TGF-β secreting cells and, therefore, resulted in a milder form of recurrent colitis. These two studies support the therapeutic use of certain strains of probiotics in different animal species to prevent and moderate diseases associated with chronic Th1 cell dominance.