## 2 IL-1 Family Cytokines, Receptors and Co-Receptors
\begin{table}
\begin{tabular}{l l l l l} \hline \hline \multirow{2}{*}{**Cytokines**} & \multicolumn{2}{l}{**Receptors (Other Names)**} & \multicolumn{2}{l}{**Co-Receptors (Other Names)**} & \multirow{2}{*}{**Function**} \\ \hline IL-1 & IL-1\(\alpha\) & IL-1R1 & & IL-1 RAcP (IL1-R3) & Pro-inflammatory \\ IL-1 & IL-1\(\beta\) & IL-1R2 & & IL-1R2 & \\  & IL-1 Ra & IL-1R1 & N/A & Antagonist \\ IL-18 & & IL-18R\(\alpha\) (IL1-R5) & IL-18R\(\beta\) (IL-18 RAcP or IL1R7) & Pro-inflammatory \\ IL-33 & & ST2 (IL-33R or IL1-R4) & IL-1 RAcP & Pro-inflammatory Th2 \\  & IL-36\(\alpha\) & IL-36R (IL-1 Rrp2 or IL-R6) & IL-1 RAcP (IL1-R3) & Pro-inflammatory \\  & IL-36 Ra & IL-36R (IL-1 Rrp2 or IL-R6) & N/A & Antagonist \\ IL-37 & & IL-18R\(\alpha\) (IL1-R5) & IL-1R8 (SIGIRR or THR8) & Antagonist \\ IL-38 & & IL-36R (IL-1 Rrp2 or ILRAPL1 (TIGIRR-2) & Antagonist/anti-inflammatory \\  & IL-1R6) IL-R9 & IL1 RAPL2 (TIGIR-1) & inflammatory \\ \hline \hline \end{tabular}  
* SIGIRR: single immunoglobulin IL-1R-related molecule; TIR: toll-IL1R; ILIRAPL1 and IL1 RAPL2: IL-1 receptor accessory protein like 1 and 2; TIGIRR 1 and 2: three immunoglobulin domain-containing IL-1 receptor-related 1 and 2.  
\end{table} 
Table 1: **IL-1 family cytokine members. **Figure 1: **Signaling pathways and regulatory mechanisms involved in the IL-1 family**. (**A**). Upon binding of IL-1\(\alpha\) and IL-\(\beta\) to their receptor IL-1R1 altogether with co-receptor IL-1 RAcP, induction of signal transduction with recruitment of myeloid differentiation primary response 88 (MyD88) accessory protein and IL-1R associated kinase (IRAK) proteins, ultimately ending in the activation of the transcription factor nuclear factor xB (NF- xB) and the transcription of proinflammatorygp genes. Regulatory mechanisms include IL-1R2 and IL-1 Ra: IL-1R2 can exist as a soluble receptor or membrane bound, acting as a decoy receptor as it is unable to recruit the co-receptor to induce signal transduction. Finally, IL-1 Ra acts as a competitive inhibitor by binding to IL-1R1. (**B**). Likewise, IL-33 binds to the receptor ST2, inducing the recruitment of co-receptor IL-1 RAcP and resulting in signal transduction into the nucleus with transcription of proinflammatorygp genes. In this family, the soluble form of ST2 also acts as a decoy receptor. IL-18 binds to IL-18R\(\alpha\) and recruits the co-receptor IL-18R\(\beta\) resulting in pro-inflammatory signaling. IL-18 binds to the soluble protein IL-18 BP preventing binding to the receptor. IL-37 is an anti-inflammatory cytokine and upon binding to IL-18R\(\alpha\) induces recruitment of the Single Ig and TIR Domain Containing (SIGIRR or IL-1R8), ultimately producing inhibitory signaling. (**C**). IL-36 cytokines also induce pro-inflammatory gene transcription by binding to the receptor IL-36R and recruiting co-receptor IL-1 RAcP. IL-36 Ra is the competitive antagonist of IL-36 cytokines. The anti-inflammatory cytokine IL-38 forms a complex with IL-36R and three immunoglobulin domain-containing IL-1 receptor-related 2 (TIGIRR-2 or IL1 RAPL1), also inducing inhibitory signaling to regulate the pro-inflammatory gene activation.