IL-18 signaling pathway (WP4754)

Homo sapiens

Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated Th1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through its binding to the IL-18 receptor complex (IL-18R) and activation of nuclear factor-kB (NF-kB), culminating in the production and release of several cytokines, chemokines, and cellular adhesion molecules. In certain cell types, IL-18 also activates mitogen-activated protein kinases (MAPKs) and PI3K/AKT signaling modules leading to the production and release of proinflammatory cytokines. IL-18 mediated signaling acts as one of the vital components of the immunomodulatory cytokine networks involved in host defense, inflammation, and tissue regeneration.


Yashwanth Subbannayya , Kristina Hanspers , Egon Willighagen , and Rex D A B


last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Homo sapiens



Pathway Ontology

Interleukin mediated signaling pathway interleukin-1 signaling pathway oxidative phosphorylation pathway signaling pathway in the adaptive immune response


Label Type Compact URI Comment
CYCS GeneProduct ncbigene:54205
BAX GeneProduct ncbigene:581
MAPK1 GeneProduct ncbigene:5594
IL-18BP GeneProduct ncbiprotein:10068
CASP8 GeneProduct ncbigene:841
NOX1 GeneProduct ncbigene:27035
TICAM2 GeneProduct ncbigene:353376
SLC12A3 GeneProduct ncbigene:6559
LCK GeneProduct ncbigene:3932
CYCS GeneProduct ncbigene:54205
NFKB1 GeneProduct ncbigene:4790
NCF1 GeneProduct ncbigene:653361
NCF2 GeneProduct ncbigene:4688
NCF1 GeneProduct ncbigene:653361
NCF2 GeneProduct ncbigene:4688
IMP3 GeneProduct ncbigene:55272
ELAVL1 GeneProduct ncbigene:1994
CTNNB1 GeneProduct ncbigene:1499
GSK3B GeneProduct ncbigene:2932
Protein GeneProduct ncbigene:11
AKT1 GeneProduct ncbiprotein:NP_005154.2
MAPK3 GeneProduct ncbigene:5595
CREB1 GeneProduct ncbiprotein:NP_604391.1
MAPK14 GeneProduct ncbiprotein:NP_001306.1
PIK3R1 GeneProduct ncbigene:5295
ELK1 GeneProduct ncbiprotein:NP_001107595.1
MAPK8 GeneProduct ncbiprotein:NP_620637.1
CHUK GeneProduct ncbigene:1147
IKBKB GeneProduct ncbigene:3551
RPS6 GeneProduct ncbiprotein:NP_001001.2
SRC GeneProduct ncbiprotein:NP_005408.1
NFKBIA GeneProduct ncbigene:4792
HSPB1 GeneProduct ncbigene:3315
CSN2 GeneProduct ncbigene:1447
MAP3K7 GeneProduct ncbigene:6885
GSK3A GeneProduct ncbiprotein:NP_002084.2
PTEN GeneProduct ncbigene:5728
ACACB GeneProduct ncbigene:32
JUN GeneProduct ncbiprotein:NP_002219.1
GRIN2B GeneProduct ncbigene:2904
PRKCA GeneProduct ncbigene:5578
PRKCB GeneProduct ncbigene:5579
RAF1 GeneProduct ncbiprotein:NP_001341618.1
TNFRSF1A GeneProduct ncbigene:7132
MEF2A GeneProduct ncbigene:4205
CEBPB GeneProduct ncbigene:1051
GATA1 GeneProduct ncbigene:2623
SP1 GeneProduct ncbigene:6667
CFLAR GeneProduct ncbigene:8837
BID GeneProduct ncbigene:637
CASP3 GeneProduct ncbigene:836
IRF1 GeneProduct ncbigene:3659
TNF GeneProduct ncbigene:7124
TP53 GeneProduct ncbigene:7157
FASLG GeneProduct ncbigene:356
FAS GeneProduct ncbigene:355
MAPK9 GeneProduct ncbigene:5601
Protein GeneProduct ncbigene:11
ELAVL1 GeneProduct ncbigene:1994
IMP3 GeneProduct ncbigene:55272
NFATC4 GeneProduct ncbigene:4776
NFKB1 GeneProduct ncbigene:4790
RELA GeneProduct ncbigene:5970
CTNNB1 GeneProduct ncbigene:1499
GSK3B GeneProduct ncbigene:2932
NFATC4 GeneProduct ncbigene:4776
RELA GeneProduct ncbigene:5970
IRAK4 GeneProduct ncbigene:12682231
MAP2K7 GeneProduct ncbigene:5609
STAT3 GeneProduct ncbiprotein:NP_644805.1
BAX GeneProduct ncbigene:581
AMPK1 GeneProduct ncbigene:5562
PARP1 GeneProduct ncbigene:142
RPS6KB1 GeneProduct ncbigene:6198
STAT3 GeneProduct ncbiprotein:NP_644805.1
PRKCD GeneProduct ncbigene:5580
IRAK1 Protein ncbigene:3654
TRAF6 Protein ncbigene:7189
IL18RAP Protein ncbigene:8807 IL18RAP
IL18 Protein ncbigene:3606
IL18R1 Protein ncbigene:8809
MYD88 Protein ncbigene:4615
IL37 Protein ncbigene:27178


  1. A comprehensive pathway map of IL-18-mediated signalling. Rex DAB, Agarwal N, Prasad TSK, Kandasamy RK, Subbannayya Y, Pinto SM. J Cell Commun Signal. 2020 Jun;14(2):257–66. PubMed Europe PMC Scholia