Identifying the roles of the microbiota, genetic susceptibility, environmental factors and specific immune cell types or cytokines and other molecules associated with IBD has led to new treatment strategies and lines of research.5
Monoclonal antibodies or biologics can neutralise pro-inflammatory cytokines such as TNF or interleukins and several are recommended in managing IBD. TNF inhibitors have a broad efficacy across a range of immune-mediated inflammatory diseases including IBD, as well as rheumatoid and psoriatic arthritis, spondylosis, psoriasis and atopic dermatitis. Biologic medicines that inhibit TNF include adalimumab, golimumab and infliximab.5,13
A particular area of interest are T-helper 17 cells (Th17), which secrete the pro-inflammatory interleukin-17. Th17 is considered currently as the main pathogenic factor in IBD, and inhibiting Th17 can decrease the development of acute colitis by reducing inflammation.1
Th17 cells develop from a range of inflammatory mediators, such as interleukins or tumour growth factors (TGF) acting on the receptors of ‘naïve’ or undifferentiated Th-cells. Reducing the level of STAT3, a signal-transducer and transcription factor protein involved in mediating the effect of several genes, can also suppress the differentiation of naïve Th-cells into Th17 cells.
Ustekinumab inhibits interleukins (IL-12 and IL-23), while vedolizumab reduces intestinal inflammation by inhibiting the Th-cells. Integrins are cell-surface proteins which allow cells to adhere to one another or to the extra-cellular matrix. Vedolizumab specifically binds to the α4β7 integrin protein on Th-cells which tend to aggregate in the gut, reducing the inflammatory response.14,15
Janus kinases (JAK) are enzymes involved in the signalling pathway with cytokines, interferons and hormones which ultimately modify proteins involved in the immune response. Tofacitinib is a JAK inhibitor.1,13