The role of IL-6 in host defence against infections: immunobiology and clinical implications

Nat Rev Rheumatol. 2017 Jul;13(7):399-409. doi: 10.1038/nrrheum.2017.83. Epub 2017 Jun 15.

Abstract

IL-6 is a pleiotropic cytokine with broad-ranging effects within the integrated immune response. One of the roles of IL-6 is to support immunocompetence, defined as the ability of a host to respond to infections. Understanding the precise role of this cytokine in immunocompetence requires a critical appraisal of data derived from both preclinical and clinical studies. Primary immunodeficiency diseases involving IL-6 or its signalling pathways reveal that IL-6 is critical in the defence against numerous types of pathogens. Studies of IL-6 signalling in preclinical models reveal that selective inhibition of either classic IL-6 signalling or IL-6 trans-signalling has differential effects on the host response to different types of infections. Knowledge of such variation might inform bioengineering of new IL-6-targeting molecules and potentially enable modulation of their toxicity. Clinical studies of IL-6 inhibitors, mainly tocilizumab, reveal that their use is associated with an increased rate of both serious and opportunistic infections generally in the range observed with other non-IL-6 directed biologic therapies. Targeting IL-6 has several other important clinical implications related to diagnosis, management and prevention of infectious diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Communicable Diseases / drug therapy*
  • Humans
  • Immunocompetence
  • Interleukin-6 / metabolism*
  • Signal Transduction

Substances

  • Antibodies, Monoclonal, Humanized
  • IL6 protein, human
  • Interleukin-6
  • tocilizumab