Table 1.
Animal Models and Human Studies Targeting the IL-1 Receptor.
| Type of Fibrosis | Role for IL-1 | References |
|---|---|---|
| Mouse Model | ||
| Pulmonary fibrosis | The administration of IL-1β to the lungs promotes inflammation and fibrosis. IL-1RA prevents this. Mice deficient in the IL-1 receptor are resistant to bleomycin-induced fibrosis. SARS-CoV-2 infection in humanized K18-hACE-2 mice treated with anakinra showed less lung fibrosis and reduced mortality. | [21,157,158] |
| Renal fibrosis | In a rat model of progressive concentric glomerulonephritis, IL-1RA stabilized glomerular injury and reduced interstitial fibrosis. Anakinra (Kineret) reduced renal fibrosis in a mouse model of salt-induced hypertension. | [159,160,161] |
| Bladder fibrosis | In an animal model of bladder fibrosis, collagen deposition was blocked with Kineret and glyburide. Glyburide inhibited the NLRP3 inflammasome, lowered secreted IL-1β and decreased fibrosis. | [162,163] |
| Cardiac fibrosis | IL-1 inhibition reduced cardiac fibrosis. | [164] |
| Skin fibrosis | In two models of scleroderma fibrosis, Anakinra significantly reduced fibrosis. IL-1β is a critical component of radiation-induced skin fibrosis. Inhibiting the IL-1 receptor with IL-1RA decreased fibrotic response in a study of deep incisional wound healing. | [165,166,167] |
| Human Studies | ||
| Erdheim-Chester | This is a rare inflammatory disease complicated by retroperitoneal fibrosis. Kineret successfully reduced fibrosis. | [168,169] |
| Rheumatoid arthritis (RA) | Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis. A review of the literature found that most biologics induced ILD in RA patients except for Kineret and hydroxychloroquine. The lifetime risk for developing RA-associated ILD was 7.7%; whereas in the normal population it was 0.9%. In a study of 1346 patients receiving Kineret, only 0.15% developed ILD. | [170,171,172] |
| Articular arthritis | Kineret was found to prevent joint fibrosis after an anterior cruciate ligament tear, returning the range of motion to normal. | [173,174,175] |
| Pulmonary fibrosis (PF) | PF secondary to COVID-19 is an expected sequelae in a subset of patients, and can be prevented with anakinra. There were decreased levels of IL-1RA in patients with PF compared to normal individuals, implicating greater IL-1 signaling. | [176,177,178] |