Table 1.
Known effects of IL-18 and IL-33 with implications for IBD pathogenesis.
| Cytokine | Experiment | Observed effect | Implication for cytokine in IBD |
|---|---|---|---|
| IL-18 | |||
| Activity blocked by IL-18 binding protein | Reduced small intestinal pathology caused by T. gondii infection ex vivo (25) | Detrimental | |
| Activity blocked by IL-18 binding protein | Attenuated DSS-colitis (26) | Detrimental | |
| Increased expression | Decreased butyrate producers in microbiota, with subsequent exacerbation of colitis (27) | Detrimental | |
| Knock-out | Protected against DNBS-induced disease in both single KO and double KO with IL-1β (28) | Detrimental | |
| Overexpression in enterocytes | GI tract overexpression promoted eosinophilic inflammation in rats (29) | Detrimental | |
| Targeted inhibition | Inflammatory mucositis alleviated in mice (30) | Detrimental | |
| Receptor knock-down | Protected against DSS-induced colitis in mice (31) | Detrimental | |
| Treatment with recombinant IL-18 | Increased neutrophil transmigration across Caco2 monolayer through Occludin loss (32) | Detrimental | |
| IL-33 | |||
| Deletion of nuclear sequestration signal | Lethal inflammation dependent on signaling through ST2 (33) | Detrimental | |
| Knock-out | Impaired recovery from extended DSS-colitis in mice (34) | Protective | |
| Receptor knock-out | Reduction in myeloid precursors of inflammation (35) | Detrimental | |
| Receptor signaling blockade | Alleviation of colitis in SAMP mice (23) | Detrimental | |
| Treatment with recombinant IL-33 | Alleviation of TNBS colitis in mice through polarization of homeostatic M2 macrophages (19) | Protective | |
| Treatment with recombinant IL-33 | Alleviation of chronic colitis in mice, reduced bacterial translocation (36) | Protective | |
| Treatment with recombinant IL-33 | Reduced colitis severity in mice in an IL-10 dependent manner (37) | Protective | |
| Treatment with recombinant IL-33 | Aggravated acute colitis (24) | Detrimental | |