Interleukin‐1a Preconditioning Reduces Myocardial Ischemia Reperfusion Injury

BackgroundInterleukin-1 (IL-1) has been shown to induce superoxide dismutase (SOD) activity and to express heat shock protein (HSP). Since the reperfusion of ischemic heart is associated with the reduction of antioxidative enzymes including SOD and expression of HSP, it was hypothesized that IL-1 could be beneficial against ischemic reperfusion injury. Methods and ResultsRats were injected with recombinant IL-1a (30 μg/kg IP); after 48 hours, they were anesthetized and hearts were removed, isolated, and perfused by the Langendorif technique. Myocardial functions were studied by measuring left ventricular developed pressure (LVDP) and its maximum first derivative (LV dP/dt), and cellular injury was studied by estimating creatine kinase (CK) release. Induction of the expression of HSP27 mRNA and HSP27 protein was examined by Western blot analysis and Northern blot analysis, respectively. Antioxidant enzymes were assayed by enzymatic analysis. Our results indicated reduction of ischemic reperfusion injury by IL-1a, as evidenced by better recovery in postischemic ventricular functions (LVDP [mm Hg]: control, 63±14; IL-1, 102+11; P<.05), increased coronary flow (mL/min) (control, 2.93± 0.58; IL-1, 5.17+0.43; P<.03), and reduced creatine kinase release (IU/L) (control, 110±5.78; IL-1, 81.76±7.71; P<.01). IL-1a induced the expression of HSP27 mRNA within 2 hours as examined by Northern blot analysis and the expression of HSP27 after 48 hours. In addition, hearts pretreated with IL-1a for 48 hours and then subjected to 30-minute ischemia and 60-minute reperfusion enhanced the activities (nmol/min/mg protein) of Cu/Zn SOD (control, 1.55±0.22; IL-ia, 2.92±0.04; P<.004), Mn-SOD (control, 4.54±0.19; IL-1a, 6.33±0.09, P<.001), catalase (control, 15.53±0.37; IL-la, 21.67±0.72; P<.002), glutathione peroxidase (control, 17.49±0.35; IL-1a, 25.87±0.58; P<.001), and glucose-6-phosphate dehydrogenase (control, 22.71±0.44; IL-ia, 29.53±0.48; P<.001). ConclusionsThe results of this study indicate that low doses of IL-la can be used as a therapeutic agent to precondition a heart from ischemia reperfusion injury.

[1]  I. Moraru,et al.  Heat Shock: A New Approach for Myocardial Preservation in Cardiac Surgery , 1992, Circulation.

[2]  N. Taniguchi,et al.  Induction of Mn-superoxide dismutase by tumor necrosis factor, interleukin-1 and interleukin-6 in human hepatoma cells. , 1992, Biochemical and biophysical research communications.

[3]  P. Rubin,et al.  Interleukin 1 alpha stimulates hemopoiesis but not tumor cell proliferation and protects mice from lethal total body irradiation. , 1991, International journal of radiation oncology, biology, physics.

[4]  I. Moraru,et al.  Role of phospholipases A2 and C in myocardial ischemic reperfusion injury. , 1991, The American journal of physiology.

[5]  D. Das,et al.  Preservation of membrane phospholipids by propranolol, pindolol, and metoprolol: a novel mechanism of action of beta-blockers. , 1990, Journal of molecular and cellular cardiology.

[6]  J. Aubin,et al.  Temporal sequence of interleukin 1 alpha-mediated stimulation and inhibition of bone formation by isolated fetal rat calvaria cells in vitro. , 1990, Cytokine.

[7]  D. Das,et al.  4 Mechanism of Free Radical Generation during Reperfusion of Ischemic Myocardium , 1990 .

[8]  A. Harken,et al.  Interleukin 1 pretreatment decreases ischemia/reperfusion injury. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. Das,et al.  Mechanism of membrane phospholipid degradation in ischemic-reperfused rat hearts. , 1989, The American journal of physiology.

[10]  B. Meyrick,et al.  Antioxidants protect cultured bovine lung endothelial cells from injury by endotoxin. , 1987, Journal of applied physiology.

[11]  J. Saklatvala,et al.  Studies on the fate of receptor-bound 125I-interleukin 1 beta in porcine synovial fibroblasts. , 1987, Journal of immunology.

[12]  P. Ghezzi,et al.  Recombinant tumor necrosis factor/cachectin and interleukin 1 pretreatment decreases lung oxidized glutathione accumulation, lung injury, and mortality in rats exposed to hyperoxia. , 1987, The Journal of clinical investigation.

[13]  S. Mizel,et al.  The interleukin 1 receptor. Dynamics of interleukin 1 binding and internalization in T cells and fibroblasts. , 1987, Journal of immunology.

[14]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[15]  J. Yodoi,et al.  Down-regulation of interleukin 1 (IL 1) receptor expression by IL 1 and fate of internalized 125I-labeled IL 1 beta in a human large granular lymphocyte cell line. , 1986, Journal of immunology.

[16]  R. Neta,et al.  Interleukin 1 is a radioprotector. , 1986, Journal of immunology.

[17]  S. Lemeshow,et al.  Cardiac performance during reperfusion improved by pretreatment with oxygen free-radical scavengers. , 1986, The Journal of thoracic and cardiovascular surgery.

[18]  W. Welch.  Phorbol ester, calcium ionophore, or serum added to quiescent rat embryo fibroblast cells all result in the elevated phosphorylation of two 28,000-dalton mammalian stress proteins. , 1985, The Journal of biological chemistry.

[19]  K. Frei,et al.  [Interleukin 1]. , 1985, Schweizerische medizinische Wochenschrift.

[20]  Y. J. Kim,et al.  Nuclear localization and phosphorylation of three 25-kilodalton rat stress proteins , 1984, Molecular and cellular biology.

[21]  E. Craig,et al.  Four small Drosophila heat shock proteins are related to each other and to mammalian alpha-crystallin. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Crapo,et al.  Preparation and assay of superoxide dismutases. , 1978, Methods in enzymology.

[23]  W. Bartley,et al.  The effect of age and sex on glutathione reductase and glutathione peroxidase activities and on aerobic glutathione oxidation in rat liver homogenates. , 1969, The Biochemical journal.

[24]  W. Valentine,et al.  Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. , 1967, The Journal of laboratory and clinical medicine.

[25]  I W SIZER,et al.  A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. , 1952, The Journal of biological chemistry.

[26]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.