Increased expression of interleukin-1β and its novel splice variant in canine hearts with volume overload

Volume overload frequently caused in dogs by chronic degenerative valvular disease (CDVD), eventually leads to cardiac failure. Experimental and clinical evidences demonstrate that increased interleukin-1β serum level in patients with heart insufficiency correlates with the severity of failure irrespective of its etiology. Very little is known about the IL-1β expression in failing vs. non-failing myocardium. IL-1β transcript level was determined in the CDVD dogs (n = 17) and control animals (n = 9) without cardiac insufficiency by real-time PCR. IL-1β transcript level in failing hearts was higher than in the control. In both groups the highest IL-1β level was detected in the left ventricles. Although IL-1β is a major pro-inflammatory cytokine most of the CDVD dogs displayed no inflammatory infiltrates into the myocardium. Massive fibrosis was observed in the control group, unlike the failing hearts, in which cardiomyocyte hypertrophy and atrophy dominated. The alternative IL-1β transcript identified here (IL-1βsv1) was significantly elevated in the failing myocardium compared with the control group. Increased IL-1β expression seems to be associated with mechanical heart overload. Its endogenous origin, and certain histopathological findings attributed to IL-1β indicate its importance in cardiac hypertrophy and failure. The lack of some typical IL-1β actions, i.e. inflammatory, pyrogenic and fibrotic, may suggest a different role of this cytokine in myocardium. It appears that the canine IL-1β gene can be transcribed in two ways in heart tissue, with the IL-1βsv1 form present mainly in failing hearts.