Anti-Cytokine Strategies beyond Anti-Tumour Necrosis Factor-α Therapy: Pathophysiology and Clinical Implications

Abstract

Cytokines are small proteins produced by a broad range of cells important in cell signaling. They include interleukins, but also chemokines, interferons, and tumor necrosis factors (TNF). They play an important role for communication between cells of the innate and adaptive immune system. The cytokine network is complex and, therefore, therapeutic interventions are difficult. The first anti-cytokine strategy successfully introduced into IBD therapy was the neutralization of TNF by antibodies. Beyond targeting this cytokine anti-IL-23 strategies were demonstrated to be of therapeutic benefit in IBD. Anti-IL-6 strategies seem to have clinical potential but also cause some risk for the patient due to the lack of CRP increase upon severe inflammation. JAK inhibitors target the intracellular signaling of several cytokine receptors and represent a promising class of broader and somewhat unspecific anti-cytokine strategies. Many other anti-cytokine approaches have failed due to the redundant nature of the cytokine network. Whether further anti-cytokines strategies have potential for IBD treatment may be evaluated in future studies.