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Interleukin-33 and Obesity-Related Inflammation and Cancer: History
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Contributor: Cameron Kowitt , Qiuyang Zhang

Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family. It is primarily associated with type 2 immune responses. It interacts with a receptor complex on immune cells in reaction to tissue damage or cellular injury. IL-33 is crucial in immune responses and is involved in various autoimmune and inflammatory diseases. Obesity is marked by chronic inflammation and is a known risk factor for several types of cancer. Recent studies have shown that IL-33 and its receptor complex are expressed in adipose (fat) tissue, suggesting they may play a role in obesity. While inflammation connects obesity and cancer, it is not yet clear whether IL-33 contributes to cancer associated with obesity. Depending on the cellular context, inflammatory environment, expression levels, and bioactivity, IL-33 can exhibit both protumorigenic and antitumorigenic effects. This review will explore the various functions of IL-33 in the inflammation linked to obesity and its relationship with cancer.

  • IL-33
  • ST2
  • immune response
  • inflammation
  • obesity
  • cancer
Interleukins (ILs), a specific subgroup of cytokines [1][2] mainly produced and secreted by white blood cells (leukocytes) and other types of cells in the body, are essential for regulating inflammation, tissue repair, and immune responses in healthy tissue [3]. The human genome encodes over 50 interleukins and related proteins [4]. ILs also help to maintain the balance and function of normal cells and tissues. Importantly, they serve as vital chemical signals in the immune system, significantly influencing cancer development, progression, and treatment. Based on their structural homology, ILs are categorized into several protein families, including IL-1, IL-2, IL-6, IL-10, IL-12, and IL-17 [4]. The IL-1 family is further divided into three subfamilies (the IL-1 subfamily, the IL-18 subfamily, and the IL-36 subfamily) based on the length of the N-terminal pro-pieces. The IL-1 subfamily consists of IL-1α, IL-1β, the IL-1 receptor antagonist (IL-1Ra), and IL-33 [5].
IL-33, discovered in 2005 as a new member of the IL-1 family [6] and confirmed to be a Nuclear Factor from High Endothelial Venules (NF-HEVs) [7], has been linked to several health conditions. These include asthma, airway inflammatory diseases [8], organ fibrosis [9], kidney injury [10], pediatric heart disease and transplantation [11], rheumatoid arthritis [12][13], and neurodegenerative diseases [14]. Recent research involving knowledge mapping of IL-33 has revealed its essential role as a cytokine in numerous diseases, especially allergic diseases [15].
Overweight and obesity are significant health issues affecting millions of people worldwide [16]. According to the World Health Statistics 2024 [17], approximately 2.5 billion adults aged 18 and older are classified as overweight, including over 890 million individuals living with obesity. This statistic indicates that around 43% of adults (43% of men and 44% of women) are overweight, with 16% facing obesity. Epidemiological studies consistently identify obesity as a significant risk factor for 13 types of cancer [18], which together account for 40% of all cancer diagnoses in the United States each year. Globally, approximately 4–8% of all cancers are linked to obesity [19]. However, the causal relationship between obesity and cancer remains unclear. Research indicates that IL-33 plays a critical role in obesity [20][21][22] and shows promising findings related to IL-33 and various cancers [23][24][25][26][27][28][29][30]. Despite this, there is a lack of research on IL-33 in the context of obesity-related cancer, particularly regarding the mechanisms by which IL-33 influences these cancers.
Gaining insight into the complex connections between IL-33, obesity, and cancer could be crucial for the future management of these conditions, offering hope in the fight against these diseases. The mechanisms may involve IL-33’s regulation of specific immune cells related to obesity that contribute to disease aggressiveness. Understanding these potential pathways and targets could guide future research and therapeutic development. Therefore, the review will discuss the importance of researching obesity-related inflammation and cancer, and potential future directions.

This entry is adapted from the peer-reviewed paper 10.3390/encyclopedia4040117

References

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