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Interleukin-1 beta, interleukin-18, and the interleukin-1 beta converting enzyme
1Department of Medicine, Division of Infectious Diseases, University of Colorado Health Science Center, Denver, Colorado 80262, USA.
Annals of the New York Academy of Sciences
|January 26, 1999
Summary
Interleukin-1 beta (IL-1 beta) and Interleukin-18 (IL-18) are potent inflammatory molecules. Both are processed by Interleukin-1 beta converting enzyme (ICE) into active forms, but only IL-1 beta is a direct pyrogen.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Interleukin-1 beta (IL-1 beta) is a potent endogenous pyrogen, but synthesized as an inactive precursor (proIL-1 beta).
- Interleukin-18 (IL-18) is structurally similar to IL-1 beta and also synthesized as an inactive precursor (proIL-18).
Purpose of the Study:
- To investigate the processing and pyrogenic activity of IL-1 beta and IL-18.
Main Methods:
- Focus on the role of Interleukin-1 beta converting enzyme (ICE, also known as caspase-1) in processing proIL-1 beta and proIL-18.
- Examined the pyrogenic effects of IL-1 beta and IL-18 in animal models.
Main Results:
- ICE cleaves intracellular proIL-1 beta to produce active, secreted IL-1 beta, a potent pyrogen.
- ICE also cleaves proIL-18 to yield an active molecule, but IL-18 is not a direct pyrogen in mice.
- IL-18 induces other inflammatory mediators like tumor necrosis factor, chemokines, and interferon-gamma.
Conclusions:
- ICE is crucial for activating both IL-1 beta and IL-18.
- While IL-1 beta directly causes fever, IL-18 contributes to inflammation and potentially fever indirectly through induction of other cytokines.