CYTOKINES AND C-REACTIVE PROTEIN-TRIGGER OF IMBALANCE OF THE HEMOSTASIS SYSTEM DURING INFLAMMATION
Journal Title: Український журнал медицини, біології та спорту - Year 2017, Vol 4, Issue 2
Abstract
Recent studies have confirmed hypothesis about crucial role of cytokines and C-reactive protein (CRP) in progression of inflammation (C.M. Ballantyne et al., 2004; B. Paimany, 2002; J.W. Steinke, 2006; J. Volanakis, 2001). Cytokines are pluripotent short-distant molecules that are synthesized by activated cells of immune system. CRP has been evaluated as «gold marker» of inflammation and predictor of various pathological states. It has been proved experimentally that pro-inflammatory cytokines such as IL-1, IL-6, IL-12, IL-3, TNF-α realized their effects through direct stimulation of CRP expression (B. Paimany, 2002). On the other hand, reaction of inflammation often results in disorders of hemostasis system. Nowadays, cytokines and CRP are considered as highly relevant factors which trigger both inflammation and hypercoagulation (T. van der Poll, et al., 2011). Nevertheless, mechanisms of the interplay between cytokines and CRP, triggering inflammation reaction and factors of hemostasis, are still unclear and require following investigations. The aim of the research was to study proinflammatory or anti-inflammatory links of cytokines’ network and CRP concentration as well as parameters of hemostasis system in conditions during inflammatory process. Materials and methods. For the research, blood samples of patients with acute inflammation (paratonsillar abscess, n=25) were used; control cohort was represented by healthy people (without acute or chronic inflammation, n=20). Parameters of hemostasis system such as fibrinogen concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR) and activity of antithrombin III (AT III) have been defined in blood plasma with the help of standard kits by routine methods. Concentrations of cytokines as IL-1β, IL-4, IL-6, IL-1RA and TNF-α have been determined in blood sera by the immunoenzyme method. CRP concentration has been defined by the turbid metric method. Statistical processing of data has been used for figures assessment (STATISTICA 10.0, Excel for Windows 10). Results and discussion. It has been found out that in blood sera of patients with paratonsillar abscess concentrations of pro-inflammatory or anti-inflammatory cytokines as well as CRP were elevated in comparison with control cohort and also results from acute inflammation process. Investigated parameters of hemostasis system have demonstrated signs of hypercoagulation in patients with paratonsillar abscess. Concentration of fibrinogen has been elevated, APTT and PT has been shortened down, and INR has been reduced (p<0.05). Elevations in fibrinogen levels are associated with an increased risk of thrombotic disease. Activation of PT in inflammation process can be regarded as evidence that cytokines are involved into activation of extrinsic mechanism of thrombin generation. Shortening of APTT has revealed that cytokines may contribute into hypercoagulation by activation of intrinsic pathway. Suppressed activity of AT III can be explained by the ability of inflammatory cytokines to decrease concentration of heparin-like molecules (M. Levi et al., 2003) which are natural cofactor of AT III and, thus, results in delayed inhibition of coagulation enzymes that is favorable for intravascular coagulation. Conclusions and prospects for further investigation. The results of our research have confirmed that elevated levels of cytokines such as IL-1β, IL-4, IL-1RA, IL-6 and TNF-α as well as CRP in inflammation are associated with imbalance of hemostasis system: Increased concentration of fibrinogen, shortening of APTT and PT, reduced INR are markers of amplification of coagulation cascade. Decreased activity of AT III sustains the suppression of anticoagulant system, and probably results from low regulation or degradation of heparin-like cofactor molecules of AT III by cytokines. These disorders of hemostasis system can be complicated by risk of thrombosis and disseminated intravascular coagulation in patients with paratonsillar abscess. Elevated concentrations of proinflammatory cytokines IL-1β, IL-6 and TNF-α as well as CRP associated with hypercoagulation may be used as predictors of DIC syndrome risk in patients with systemic inflammation.
Authors and Affiliations
Hady Al-Rihani, Irina Karmazina
Keywords
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