Recent advances in immunology enabled the characterization of several signal transmitting pathways responsible for proper cytokine and chemokine signaling. Among them, Janus kinases (JAKs) are essential components of receptor activation systems. The discovery of JAK kinases enabled the synthesis of JAK kinase inhibitors (JAKi or Jakinibs), which have proven to be efficacious in the treatment of hematologic malignancies and several rheumatological disorders and continue to be investigated in many clinical indications. Blocking multiple cytokines belonging to several cytokine families with a single small molecule may, however, create a potential risk for the patients. Recently, a higher risk of thromboembolic complications, namely, deep vein thrombosis and pulmonary embolism, has been recognized as the main concern during treatment with Jakinibs. At present, it is not entirely clear whether this increased risk is related to direct cytokine blockade, the presence of concomitant diseases in treated patients or other unknown circumstances that work together to increase the risk of this side effect. In this review, we discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk. Many indirect data indicate that higher thromboembolic risk may be related to the specificity of JAK inhibitor action, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.

Objective.: To study the influence of anti-tumor necrosis factor-α (TNF-α) treatment on echocardiographic measures and concentrations of endothelin 1 (ET-1), interleukin 6 (IL-6), and amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a cohort of 23 female patients with rheumatoid arthritis (RA).Methods.: We recruited 23 patients (mean age 51.3 ± 1.55 yrs) with RA resistant to treatment with disease-modifying antirheumatic drugs and average disease duration of 7.1 ± 1.0 years who had been selected to start treatment with the anti-TNF-α antagonist infliximab. Transthoracic echocardiographic examinations were performed before the first infusion and repeated after 1 year of treatment. Data for age, sex, RA disease activity by Disease Activity Score (DAS28) and echocardiographic data, NT-proBNP, IL-6, ET-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other routine laboratory data were collected before treatment and after 1 year.Results.: Twelve months of treatment with infliximab resulted in reduction of RA activity (i.e., reduction of DAS and acute-phase reactants). There was increased left ventricle ejection fraction, from 58.5% before treatment to 63% after. Treatment with infliximab also resulted in significant reduction of ET-1 (1.26 fmol/ml before treatment vs 0.43 fmol/ml after), IL-6 (58.46 pg/ml vs 3.46 pg/ml), and NT-proBNP (43.06 fmol/ml vs 14.78 fmol/ml). These reductions were observed after just 4 months of treatment and remained significant until the termination of the study.Conclusion.: In patients with RA, treatment with infliximab contributed significantly to increase in left ventricular ejection fraction. Improvement of cardiac function was shown by conventional echocardiography; there was reduction of biochemical markers of heart failure.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease. Up to one-third of patients suffering from SLE have various ocular manifestations. The ocular findings may represent the initial manifestation of the systemic disease and may lead to severe ocular complications, and even loss of vision. Ocular manifestations are often associated with degree of systemic inflammation, but also can precede the occurrence of systemic symptoms. Early diagnosis and adequate management of patients with SLE are crucial and require cooperation between various specialists. Proper preparation of ophthalmologists can help to differentiate between complication of SLE and other ocular disorders. New therapies for SLE are promising for potential benefits, however, ocular side effects are still unknown.

Janus kinase (JAK) inhibitors, a novel class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), have shown their safety and efficacy in rheumatoid arthritis (RA) and are being intensively tested in other autoimmune and inflammatory disorders. Targeting several cytokines with a single small compound leads to blocking the physiological response of hundreds of genes, thereby providing the background to stabilize the immune response. Unfortunately, blocking many cytokines with a single drug may also bring some negative consequences. In this review, we focused on the activity of JAK inhibitors in the cardiovascular system of patients with RA. Special emphasis was put on the modification of heart performance, progression of atherosclerosis, lipid profile disturbance, and risk of thromboembolic complications. We also discussed potential pathophysiological mechanisms that may be responsible for such JAK inhibitor-associated side effects.

Treatment with anti-TNF-α (tumor necrosis factor), one of the pivotal cytokines, was introduced to clinical practice at the end of last century and revolutionized the treatment of rheumatoid arthritis (RA) as well as many other inflammatory conditions. Such a treatment may however bring many safety issues regarding infections, tuberculosis, as well as cardiovascular diseases, including heart failure. Given the central role of proinflammatory cytokines in RA, atherosclerosis, and congestive heart failure (CHF), such a treatment might result in better control of the RA process on the one side and improvement of heart function on the other. Unfortunately, at the beginning of this century two randomized controlled trials failed to show any benefit of anti-TNF treatment in patients with heart failure (HF), suggesting direct negative impact of the treatment on morbidity and mortality in HF patients. As a result the anti-TNF treatment is contraindicated in all patients with heart failure and a substantial portion of patients with RA and impaired heart function are not able to benefit from the treatment. The role of TNF in CHF and RA differs substantially with regard to the source and pathophysiological function of the cytokine in both conditions, therefore negative data from CHF studies should be interpreted with caution. At least some of RA patients with heart failure may benefit from anti-TNF treatment, as it results not only in the reduction of inflammation but also contributes significantly to the improvement of cardiac function. The paper addresses the epidemiological data of safety of anti-TNF treatment in RA patients with the special emphasis to basic pathophysiological mechanisms via which TNF may act differently in both diseases.