The Interleukin-1 (IL1) family of cytokines comprises 11 members, namely Interleukin-1 alpha (IL1A), Interleukin-1 beta (IL1B), Interleukin-1 receptor antagonist protein (IL1RN, IL1RA), Interleukin-18 (IL18), Interleukin-33 (IL33), Interleukin-36 receptor antagonist protein (IL36RN, IL36RA), Interleukin-36 alpha (IL36A), Interleukin-36 beta (IL36B), Interleukin-36 gamma (IL36G), Interleukin-37 (IL37) and Interleukin-38 (IL38). The genes encoding all except IL18 and IL33 are on chromosome 2. They share a common C-terminal three-dimensional structure and with apart from IL1RN they are synthesized without a hydrophobic leader sequence and are not secreted via the classical reticulum endoplasmic-Golgi pathway.
IL1B and IL18, are produced as biologically inactive propeptides that are cleaved to produce the mature, active interleukin peptide.
The IL1 receptor (IL1R) family comprises 10 members: Interleukin-1 receptor type 1 (IL1R1, IL1RA), Interleukin-1 receptor type 2 (IL1R2, IL1RB), Interleukin-1 receptor accessory protein (IL1RAP, IL1RAcP, IL1R3), Interleukin-18 receptor 1 (IL18R1, IL18RA) , Interleukin-18 receptor accessory protein (IL18RAP, IL18RB), Interleukin-1 receptor-like 1 (IL1RL1, ST2, IL33R), Interleukin-1 receptor-like 2 (IL1RL2, IL36R), Single Ig IL-1-related receptor (SIGIRR, TIR8), Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1, TIGGIR2) and X-linked interleukin-1 receptor accessory protein-like 2 (IL1RAPL2, TIGGIR1). Most of the genes encoding these receptors are on chromosome 2.
IL1 family receptors heterodimerize upon cytokine binding. IL1, IL33 and IL36 bind specific receptors, IL1R1, IL1RL1, and IL1RL2 respectively. All use IL1RAP as a co-receptor. IL18 binds IL18R1 and uses IL18RAP as co-receptor.
The complexes formed by IL1 family cytokines and their heterodimeric receptors recruit intracellular signaling molecules, including Myeloid differentiation primary response protein MyD88 (MYD88), members of he IL1R-associated kinase (IRAK) family, and TNF receptor-associated factor 6 (TRAF6), activating Nuclear factor NF-kappa-B (NF?B), as well as Mitogen-activated protein kinase 14 (MAPK14, p38), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs) and other Mitogen-activated protein kinases (MAPKs).