**3. Materials and methods**

triad of symptoms: swelling, proteinuria, and hypertension and in severe cases, convulsions and coma [1, 2]. Preeclampsia remains one of the most sophisticated problems of modern obstetrics and gynecology. It generally determines the structure of maternal and perinatal morbidity and mortality. The role of immune mechanisms contributing to the development of a normal pregnancy is widely discussed. Their involvement in the pathogenesis of pregnancy complications such as preeclampsia was also noted [3]. The analysis of the scientific literature reveals the conclusion that many aspects of the pathogenesis of preeclampsia are related with systemic inflammatory response syndrome with the development of a destructive inflammatory process, immune disorders, and the imbalance of cytokine regulation of gestation

The role of vascular endothelial damage with the development of generalized arteriolar spasm as one of the leading mechanisms in the pathogenesis of preeclampsia is supposed to be significant. However, the relationship between the development of endothelial dysfunction and disruption of cytokine regulation in different clinical forms of preeclampsia also

Proteinuria has been proposed and studied as both an indicator of the severity of the disease and a predictor of the outcome in preeclampsia. Many clinicians still make major manage-

Cytokines, such as IL-2, IL-8, and TNF-α, are pro-inflammatory, increased in the blood, in leukocytes during PE. Elevated concentrations of TNF-α have been observed in the blood of women with PE [8]. Further studies support the idea of the involvement of the maternal immune system in the development of preeclampsia which comes from the prim paternity theory [9]. This hypothesis holds that the risk of developing preeclampsia is highest in the first pregnancy [10], and a previous normal pregnancy is associated with a lowered incidence

In contrast to normal pregnancy, there are indications of increased inflammatory responses [12] and also of an immune deviation toward Th1 in the established preeclampsia pregnancy [13]. Roberts et al. [14] were one of the first to suggest that mediators released in preeclampsia are responsible for the endothelial damage seen in preeclampsia. Subsequent to the damage, the injured endothelium initiates a dysfunctional cascade of coagulation, vasoconstriction, and intravascular fluid redistribution that results in the clinical syndrome

Numerous studies show that the balance of cytokines has special importance in the regulation of pregnancy. However, the diagnostic and prognostic significance of breaches in the immune

The purpose of the actual study was to evaluate the relationship between the formation of anti-inflammatory cytokines and several indicators of moderate and severe preeclampsia in

requires further research and is currently represented in several scientific works [7].

ment decisions based on the degree of proteinuria in these patients.

of preeclampsia [11] in the subsequent pregnancy.

balance during preeclampsia has not yet been determined.

processes [4–6].

148 Autoantibodies and Cytokines

of preeclampsia [15].

the third trimester of pregnancy.

**2. Aim**

We conducted a prospective study of 50 women with pregnancies complicated by varying degrees of preeclampsia in the third trimester of gestation with singleton pregnancies between 28 and 40 weeks' gestation (±1 week), parity (parity 1 l–4 and parity > 4), and maternal age (<20 years, 20–35, and >35 years) and in 50 normotensive patients without threatening signs of hypertension and preeclampsia, hospitalized at the University Clinic of Gynecology and Obstetrics, Skopje, Republic of Macedonia.

The severity of preeclampsia was determined according to the definition of the *WHO Handbook for Guideline Development*, Geneva, 2010. Our inclusion criteria were reproductive age, diagnosed moderate and severe preeclampsia based on the criteria for classification at the time of collection of maternal serum, and the patients' informed consent for inclusion in the survey.

Exclusion criteria were acute and chronic genital and extra genital diseases (essential hypertension, heart failure, diabetes, morbid obesity, immunodeficiency, systemic diseases, chronic infectious diseases, genetic pathology).

Patients with preeclampsia were categorized into moderate (m PE) group A and severe (S PE) preeclampsia group B according to the degree of preeclampsia.

Cytokine levels in the serum were measured by the "sandwich" method of solid-phase enzyme immunoassay using double antibody. As a standard for comparison of each reaction, recombinant cytokines were used, which are part of the test—whale.

Statistical data processing was done using the SPSS 13.0 software for Windows.
