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Novel targets for interleukin 18 binding protein
1Department of Medicine, University Colorado Health Sciences Centre, Denver 80262, USA.
Annals of the Rheumatic Diseases
|March 14, 2002
Summary
Interleukin 18 binding protein (IL18BP) significantly improved myocardial contractile function following ischemia/reperfusion injury. IL18BP treatment preserved tissue creatine kinase levels and attenuated contractile force depression, highlighting its therapeutic potential.
Area of Science:
- Cardiovascular Biology
- Immunology
- Molecular Medicine
Background:
- Interleukin 18 (IL18) is a pro-inflammatory cytokine structurally and functionally related to the IL1 family.
- IL18 is synthesized as an inactive precursor requiring cleavage by caspase-1 (ICE) for activation.
- Interleukin 18 binding protein (IL18BP) acts as a natural high-affinity inhibitor of IL18 activity.
Purpose of the Study:
- To investigate the role of IL18 in human myocardial function.
- To assess the therapeutic potential of IL18BP in mitigating ischemia/reperfusion (I/R) induced myocardial dysfunction.
Main Methods:
- Utilized an in vitro ischemia/reperfusion (I/R) model using suprafused human atrial myocardium.
- Assessed myocardial contractile force and intracellular tissue creatine kinase levels.
- Investigated the effects of IL18BP administration and ICE inhibition on myocardial function post-I/R.
Main Results:
- IL18BP treatment improved post-I/R contractile function from 35% to 76% of control levels.
- IL18BP preserved intracellular tissue creatine kinase levels by 420%.
- Inhibition of ICE, which is required for IL18 activation, also attenuated the depression in contractile force.
Conclusions:
- Myocardial ischemia is a pathological process targeted by IL18BP.
- IL18BP demonstrates significant potential in reducing ischemia-induced myocardial dysfunction.
- Targeting IL18 activity via IL18BP represents a promising therapeutic strategy for cardiovascular protection.