TY - JOUR
T1 - The role of IL-6 in host defence against infections
T2 - Immunobiology and clinical implications
AU - Rose-John, Stefan
AU - Winthrop, Kevin
AU - Calabrese, Leonard
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85021014942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021014942&partnerID=8YFLogxK
U2 - 10.1038/nrrheum.2017.83
DO - 10.1038/nrrheum.2017.83
M3 - Review article
C2 - 28615731
AN - SCOPUS:85021014942
SN - 1759-4790
VL - 13
SP - 399
EP - 409
JO - Nature Reviews Rheumatology
JF - Nature Reviews Rheumatology
IS - 7
ER -