What is the clinical evidence from this study?

Study design: Other. Population: Myocardial inflammation. Intervention: Interleukin-1 beta (IL-1β) vs. Control. Primary outcome: [3H]leucine incorporation (p=<0.001).

August 1, 1995Open Access

Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes.

Q: What are the key findings of this study?

Interleukin-1 beta increased [3H]leucine incorporation by 30% and net cellular protein content by 20% in cultured neonatal rat cardiac myocytes, inducing hypertrophy without DNA synthesis.

Key Result

Interleukin-1 beta increased [3H]leucine incorporation by 30% and net cellular protein content by 20% in cultured neonatal rat cardiac myocytes, inducing hypertrophy without DNA synthesis.

Structured PICO

Population

Cultured myocytes from neonatal rat hearts and ventricular myocardium from adult rats

Intervention

IL-1 beta (2 ng/ml for 24 h) in vitro; lipopolysaccharide (4 mg/kg intraperitoneally for 18 h) in vivo

Comparator

Untreated controls (implied)

Outcome

Myocyte growth ([3H]leucine incorporation, net cellular protein content, DNA synthesis) and phenotype (mRNA levels of ANF, beta-MHC, SERCA2, CRC, and VDCC)surrogate

IL-1 beta induces cardiac myocyte hypertrophy and alters gene expression toward a fetal phenotype while downregulating calcium regulatory genes via a nitric oxide-independent mechanism.

Main Result

p-value: p=<0.001

Limitations

In vitro model using neonatal cells may not fully represent adult myocytes
Presence of a small percentage of nonmyocytes (fibroblasts) in the culture could potentially mediate some effects
In vivo LPS model induces multiple cytokines, so effects cannot be solely attributed to IL-1β
Unclear if changes in steady-state mRNA levels translate to altered protein levels

Abstract

Mononuclear cell infiltration and local cytokine elaboration are hallmarks of inflammatory and immunologic heart diseases. To test the hypothesis that cytokines can modulate cardiac myocyte growth and phenotype, myocytes cultured from neonatal rat hearts were exposed to IL-1 beta, an inflammatory cytokine prevalent in myocardial inflammation. IL-1 beta (2 ng/ml, 24 h) increased 3Hleucine incorporation by 30 +/- 4% (P 10-fold, n = 4), and decreased mRNA levels for sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) (-46 +/- 7%; P < 0.001; n = 11), calcium release channel (CRC) (-65 +/- 11%, P < 0.001, n = 8) and voltage-dependent calcium channel (VDCC) (-53 +/- 7%, P < 0.001, n = 8). NG-monomethyl-L-arginine (1 mM), an inhibitor of nitric oxide (NO) synthesis, did not inhibit the IL-1 beta-induced protein synthesis or changes in mRNA levels. In ventricular myocardium obtained from adult rats treated with lipopolysaccharide (4 mg/kg intraperitoneally 18 h) to stimulate systemic cytokine production, there were changes in the mRNA levels for beta-MHC (6 +/- 1-fold, P < 0.01, n = 4), SERCA2 (-65 +/- 4%, P < 0.0001, n = 4), CRC (-67 +/- 5%, P < 0.001, n = 4), and VDCC (-58 +/- 5%, P < 0.001; n = 4) that were qualitatively similar to those observed in cultured myocytes. Thus, IL-1 beta, acting via an NO-independent mechanism, caused myocyte hypertrophy associated with induction of fetal genes (ANF and beta-MHC) and downregulation of three important calcium regulatory genes (SERCA2, CRC, and VDCC). IL-1 beta may contribute to the abnormal structural and functional alterations of cardiac myocytes in conditions marked by mononuclear cell infiltration.

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