Antibodies against Chlamydia pneumoniae in stable angina and interleukin-6 levels

International Journal of Cardiology 88 (2003) 99–100 www.elsevier.com/locate/ijcard Letter to the Editor A ntibodies against Chlamydia pneumoniae in stable angina and interleukin-6 levels * ˜˜ ´´ ´ ´ Candelas Gonzalez-Castaneda, Jose-Luis Perez-Castrillon , Marıa-Luisa Arranz-Pena, ´ Victor Gonzalez, Vicente Herreros-Fernandez Department of Internal Medicine , University Hospital Rio Hortega , Valladolid , Spain Received 30 January 2002; accepted 6 April 2002 Keywords : Chlamydia pneumoniae; Inflammation; Atherogenesis; Coronary heart disease Inflammation is a key mechanism in atherogenesis phase reactants (fibrinogen, C-reactive protein). and the rapid progression of coronary artery disease. Chronic infection may also increase the expression of Tissue lesion occasions the release of chemical procoagulants derived from the monocytes, such as mediators, cytokines, accompanied by an increase in tissular factor and, therefore, increase the risk of the blood concentrations of acute phase reactants, localized thrombosis or embolization [3]. The object such as fibrinogen, C-reactive protein, serum amyloid of our study was to evaluate whether or not the A protein, sialic acid and ceruloplasmin and a positivity of antibodies against C . pneumoniae modireduction of those of albumin. It has been observed fied interleukin-6 levels in a group of patients with that these proteins are higher in patients with isstable angina chemic heart disease and, furthermore, who have a IL-6 was determined in a group of patients (36 higher tendency to present adverse cardiovascular males and 15 females) with stable angina. The incidents [1]. On the other hand, the inflammation inclusion criteria of stable angina was defined accordappears to be directly linked to the ‘vulnerability’ or ing to the Spanish Society of Cardiology. For the ‘instability’ of the atheromatous plaques that precontrol group, 27 blood samples were taken from dispose to disruption and acute coronary incidents. healthy donors and people who submitted to analytic The inflammatory mechanism, therefore, can reprecontrols. Interleukin-6 was determined by ELISA sent the final common connection channel of chronic technique (enzyme-linked immunoabsorbent assay) in infection between atherogenesis and the clinical blood samples (Human ELISA IL-6 Endogen Inc., manifestations of coronary artery disease [2]. Woburn, MA, USA), with a coefficient of variation Infection by C . pneumoniae can induce a chronic (CV) of 2–5%. Anti-Chlamydia pneumoniae IgG immune activation mediated by cytokines, which were determined by the micro-immunofluorescence directly contribute to the chronic damage of the (micro-IF) test. The patients were stratified in two endothelial cell or stimulate the synthesis of acute groups according to antibody titer: group 1 in which no anti-C . pneumoniae antibodies (seronegative) were detected and group 2 with a titer above 1/64 * Corresponding author. ´´ E-mail address : [email protected] (J.-L. Perez-Castrillon). (seropositive). 0167-5273/02/$ – see front matter  2002 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0167-5273(02)00383-2 ˜ 100 C . Gonzalez-Castaneda et al . /International Journal of Cardiology 88 (2003) 99–100 The statistical analysis was made by a Pentium II constituting a systemic marker of inflammation that computer using the SPSS 9.0 statistics program using facilitates passage of an arteriosclerotic lesion to a a Fisher’s test, chi-square test, the Mann–Whitney vulnerable plaque. This data differs from the results U-test.The study conformed to the norms of the obtained by other researchers, the majority of whom Hospital Ethics Committee and in accordance with detected an increase in IL-6 in situations of instability the Helsinki Declaration. or stress, unstable angina and acute myocardial No statistically significant association was found in infarction.Vergassola et al. [6] likewise observed very the group with stable angina between the IL-6 values high levels of IL-6 in 100% of the 17 patients studied and the presence (IL-6: 0.4560.37 pg/ml, n530) or with acute myocardial infarction, as opposed to absence (IL-6: 0.3760.52 pg/ml, n521) of antidetectable levels of said cytokine in the control bodies against C . pneumoniae. A statistically signifigroup. They also detected a good correlation between cant association of P50.001, calculated by the the IL-6 levels and the IgA antibody against C . Mann–Whitney test, did exist between IL-6 levels of pneumoniae. We did not find these correlation, althe cases represented by a group of patients with though we did not determine IgA antibodies. Studies stable ischaemic heart disease and those of the of a larger population are necessary in order to control group of persons without ischaemic heart evaluate the possible role of Chlamydia pneumoniae disease pathology. In this group the levels was in the induction of IL-6. undetectable and 0.042 pg/ml in the first group. There are some studies that support the relation between C . pneumoniae and IL-6. Kaukoranta et al. R eferences [4] demonstrated in vitro that C . pneumoniae inocu- ´´ lated into mononuclear cells of peripheral human [1] Garcia-Moll X, Kaski JC. Cardiopatıa isquemica: marcadores de ´ inflamacion y riesgo cardiovascular. Rev Esp Cardiol 1999;52:990– blood grew in the cells and induced the secretion of 1003. cytokines, IL-6 among them. The cytokine response [2] Kaski JC, Cox ID. Chronic infection and atherogenesis. Eur Heart J was concentration-dependent, although it is not 1988;19:366–7. [3] Gupta S, Camm AJ. Chlamydia pneumoniae and coronary heart known if the intracellular growth of the C . pneumo-disease. Coincidence, association, or causation? Br Med J niae plays a role in the induction of cytokines. Along 1997;314:1778–9. the same line, Heineman et al. [5] demonstrated that [4] Kaukoranta-Tolvanen SSE, Teppo AM, Laitinen K et al. Growth of Chlamydia pneumoniae in cultured human peripheral blood monoC . pneumoniae grows in the monocytic cells and that nuclear cells and induction of a cytokine response. Microb Pathog it is a strong inductor among other cytokines of IL-6. 1996;21:215–21. In our study no statistically significant association [5] Heinemann M, Susa M, Simnacher U et al. Growth of Chlamydia was observed between seropositivity for C . pneumo-pneumoniae induces cytokine production and expression of CD14 in a human monocyte cell line. Infect Immun 1996;64:4872–5. niae and the IL-6 level but there was difference [6] Vergassola R, Mazzoli S, Fantini A et al. Anti-Chlamydia pneumobetween the group of patients with stable angina and niae antibodies and production of interleukin 6 in acute myocardial the control group. Our results support the hypothesis infarction. Ital Cardiol 1997;27:470–5. that in the pathogenesis of ischaemic heart disease, an inflammatory mechanism may intervene, the IL-6