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Abstract
Summary
Heart failure is common medical problem, it is the main cause of hospital admissions in elderly individuals and represents the commonest diagnosis in cardiology medical awards. Heart failure is a common problem associated with considerable mortality and morbidity. (Birks and Yocoub, 1997)
Cytokines are highly potent, pleiotropic, endogenous peptides produced by a variety of cell types. (Oppenheim, et al., 1989)
Cytokines are being increasingly recognized as important factors in the pathogenesis and pathophysiology of heart failure. Elevated levels of circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo (Matsumori,1997)
Recent evidence suggests that proinflammatory cytokines are capable of modulating cardiovascular function by a variety of mechanisms, such as promoting left ventricular remodeling (Pagan et al., 1992), inducing contractile dysfunction (Finkel et al., 1992), and uncoupling myocardial beta - adrenergic receptors. (Fowler, et al., 1986)
Studies proved that Interleukin-6 can modify the ventricular function through increase of nitrate oxide syntheses. (Finken, et al., 1992)
So understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure with the use of monoclonal antibodies directed against specific cytokines that may block the downhill progression of heart failure. (Blum and Miller, 1998)
So the aim of this study is to assess the serum level of IL-6 in patients with heart failure and to study the relationship between serum level of IL-6 and NYHA functional classes heart failure of different causes.
This study was carried out in cardiology department faculty of medicine, Zagazig university and Cairo university hospitals from 1999 to 2003.
Our study included 10 normal persons and 43 patients having a chronic heart failure and there age ranged from 45 years to 83 years, they were 35 male and 8 female. They were classified according to CHF NYHA classification into:
a) group I : included 10 normal persons (3 female and 7 male)
b) group II : included 11 patients chronic CHF class- II (2 female and 9 male)
c) group III : included 12 patients chronic CHF class - III (2 female and 10 male)
d) group IV : included 20 patients chronic CHF class – IV (4 female and 16 male)
* Our patients were (43 patients) there were,
- 13 patients had hypertension (30.2%)
- 9 patients had diabetes mellitus, (20.9%)
- 28 patients had ischaemic cardiomyopathy, (65.1%)
- 12 patients had dilated cardiomyopathy, (27.9%)
- 4 patients had coronary artery bypass graft (CABG), (9.3%)
- 12 patients had valvular heart diseases (27.9%)
We excluded the following patients from the study :
1) Patients received antinflammatory or corticosteroid within the preceding 2 weeks before sampling.
2) Patients with concomitant diseases as.
a) Acute coronary syndrome (ACS) at least 3 months before sampling.
b) Infections c) Rheumatic fever d) Malignancy e) Thyroid diseases
f) Collagen diseases g)Pulmonary diseases h) Kidney diseases as
renal failure.
All patients in the study were subjected to:
A full history and thorough clinical examination. , Standard 12 – lead resting ECG ,and Echocardiography.
Interleukin-6 was measured by ELISA kit Supplied form *Biosource.
The Biosource IL-6 is a solid phase Enzyme Amplified Sensitiving Immunoassay (LASLY) performed plate. (Houssiar, FA et al., 1988)
The data was coded and entered on an IBM compatible computer using the statistical package SPSS (SPSS / PC ver 5, 1992).
We found in our study that:
- There was no relationship between the patients’ age and serum IL-6 level. This result is in agreement with (Efthymios, et al., 2000) and (Mariop et al., 2000)
- There is statistically non significant difference among the studied groups in patients’ blood pressure, heart rate and temperature on the level of IL-6.
- Also there is statistically non significant difference in serum IL-6 level between male and female
- We studied the laboratory data among studied groups and we found that the mean value of blood urea, creatinine, sodium and potassium among the studied groups were within normal limits and there is statistical non significant relationship between serum IL-6 level and different level of urea, creatinine, sodium and potassium.
The echocardiographic data of our study was.
- According to the degree of CHF NYHA classification there is statistically significant difference increased in end diastolic diameter
(EDD) and end systolic diameter (ESD) in patients had CHF class II , III and IV .compared to group I (normal persons) (p-value = 0.001).
- And there was a statistically significant positive correlation between end systolic diameter (ESD) and serum IL-6 level. (p-value = 0.029), And this result was disagreement with that done by (Hakan Oral, et al., 2003).
- Also there was statistically non significant correlation between the plasma levels of IL-6 and left ventricle end diastolic volume (EDD) (P-value = 0.291) and this result was in agreement with that done by (Hakan Oral, et al., 2003).
- There was statistically significant negative correlation between fractional shortening (FS) and the serum level of IL-6 (p-value = 0.053). And this result was disagreement with that done by (Hakan Oral, et al., 2003).
- There was statistically non significant correlation between ejection fraction (EF) and the serum level of IL-6 (P-value = 0.139) and this result was in agreement with that done by (Hakan Oral, et al., 2003)
- We found that IL-6 serum level was markedly elevated in heart failure group IV compared to heart failure group III compared to heart failure group II compared to normal persons. (P-value = 0.001)
- We studied the serum IL-6 level in different etiological causes of heart failure and the results were as the fallow:
- In hypertensive patients (13 patients,) the serum IL-6 level was statistically non significant compared to non hypertensive patients (30 patients) (p-value = 0.63), and this result was disagreed with other studies as (Hakan Oral, et al., 2003), (Chae, et al., 2001) and (Furumoto T, et al., 2002)
- In patients with diabetes mellitus (D.M) (9 patients) serum IL-6 level was statistically non significant compared to non diabetic patients (34 patients) (p-value = 0.67). These results were disagreement with (Kauffmann, et al., 1994) and (Mujazzuki, et al., 1995).
- Also serum level of IL-6 in patients of heart failure with ischaemic cardiomyopathy (ICM) (28 patients) was statistically non significant compared to non ischaemic cardiomyopathy patients (15 patients). (p-value = 0.17).
- The serum IL-6 level in patients having dilated cardiomyopathy (12 patients) was statistically non significant compared to non dilated cardiomyopathy patients (31 patients) (p-value = 0.72), This result was in agreement with that done by (Munger, et al., 1996) and (Chi- jen et al., 2003)
- The number of patients having valvular heart diseases were 12 patients as an etiological cause of heart failure and the serum IL-6 level was statistically non significant compared to 31 patients not having valvular heart diseases (p-value = 0.63),and this result was in agreement with that dome by (Chi-jeni, et al., 2003) .
In general there was statistically non significant different in serum
IL-6 level in patients with heart failure as regard as the etiological causes of heart failure. These results are agreement by (Munger, et al., 1996), (Akrust p, et al., 1999), (Mac Gowan, et al., 1997) and (Chi-jeni, et al., 2003).