Transforming growth factor-beta and
interleukin 10 have diverse immune inhibitory properties that have restored homeostatic defense mechanisms in experimental models of
autoimmune disease. The goals of this review are to describe the actions of each
cytokine, review their investigational use in animal models and patients, and indicate their prospects as interventions in
autoimmune hepatitis. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed.
Transforming growth factor-beta expands the natural and inducible populations of regulatory T cells, limits the proliferation of natural killer cells, suppresses the activation of naïve CD8+ T cells, decreases the production of
interferon-gamma, and stimulates fibrotic repair.
Interleukin 10 selectively inhibits the CD28 co-stimulatory signal for
antigen recognition and impairs
antigen-specific activation of uncommitted CD4+ and CD8+ T cells. It also inhibits maturation of dendritic cells, suppresses Th17 cells, supports regulatory T cells, and limits production of diverse pro-inflammatory
cytokines. Contradictory immune stimulatory effects have been associated with each
cytokine and may relate to the dose and accompanying
cytokine milieu. Experimental findings have not translated into successful early clinical trials. The recombinant preparation of each agent in low dosage has been safe in human studies. In conclusion,
transforming growth factor-beta and
interleukin 10 have powerful immune inhibitory actions of potential therapeutic value in
autoimmune hepatitis. The keys to their therapeutic application will be to match their predominant non-redundant function with the pivotal pathogenic mechanism or
cytokine deficiency and to avoid contradictory immune stimulatory actions.