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(Circulation. 2004;110:II-219 – II-224.)
© 2004 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Role of Interleukin-1ß in Acute Inflammation and Graft Death After Cell Transplantation to the Heart

Ken Suzuki, MD PhD; Bari Murtuza, MD PhD; Jonathan R. Beauchamp, PhD; Nigel J. Brand, PhD; Paul J. R. Barton, PhD; Anabel Varela-Carver, PhD; Satsuki Fukushima, MD; Steven R. Coppen, PhD; Terence A. Partridge, PhD; Magdi H. Yacoub, FRS

From the Harefield Heart Science Centre (K.S., B.M., N.J.B., P.J.R.B., A.V.-C., S.F., S.R.C., M.H.Y.), National Heart and Lung Institute, Imperial College London, Harefield, Middlesex, United Kingdom; Muscle Cell Biology Group (J.R.B., T.A.P.), MRC Clinical Science Centre, Hammersmith Hospital, Imperial College London, London, United Kingdom.

Correspondence to Dr. Ken Suzuki, Cell and Gene Therapy Group, Harefield Heart Science Centre, Harefield, Middlesex, UB9 6JH, UK. E-mail k.suzuki{at}ic.ac.uk

Background— Poor survival of grafted cells is a major factor hindering the therapeutic effect of cell transplantation; however, the causes of cell death remain unclear. We hypothesized that interleukin-1ß (IL-1ß) might play a role in the acute inflammatory response and graft death after cell transplantation and that inhibition of IL-1ß might improve graft survival.

Methods and Results— ¹⁴C-labeled male skeletal muscle precursor cells were implanted into female mouse hearts by direct intramuscular injection. The amount of ¹⁴C-label provides an estimate of the surviving cell number, whereas the amount of male-specific Smcy gene measured by polymerase chain reaction indicates the total (surviving+proliferated) number of donor-derived cells. At 10 minutes after implantation, 44.8±2.4% of the grafted cells survived and this steadily decreased to 14.6±1.1% by 24 hours, and to 7.9±0.6% by 72 hours (n=6 in each point). Proliferation of the surviving cells, which began after 24 hours, resulted in an increase in the total cell number from 15.5±0.8% at 24 hours to 24.4±1.6% at 72 hours. Acute inflammation was prominent at 24 hours and was reduced by 72 hours, in parallel with IL-1ß expression. Administration of anti-IL-1ß antibody improved graft survival at both 24 (25.6±1.6%) and 72 hours (14.8±1.1%) and resulted in a 2-fold increase in the total cell number at 72 hours (45.8±2.4%). The effects of IL-1ß inhibition corresponded with a reduced inflammatory response.

Conclusion— IL-1ß is involved in acute inflammation and graft death after direct intramyocardial cell transplantation. Targeted inhibition of IL-1ß may be a useful strategy to improve graft survival.

Key Words: cell transplantation • skeletal myoblast • interleukin-1ß • inflammation • survival