Rheumatoid arthritis (RA) is classified as an inflammatory, chronic autoimmune and disabling disease based on the intricate interplay between environmental and genetic factors. With a prevalence ranging from 0.3 to 1%, RA is the most prevalent inflammatory joint disease observed in adults. Disruption of immune tolerance becomes evident when abnormal stimulation of the innate and adaptive immune system occurs. This cascade of events causes persistent joint inflammation, proliferative synovitis and, ultimately, damage of the underlying cartilage as well as the subchondral bone, leading to permanent joint destruction, deformity and subsequent loss of function. With cytokines being the key to a multitude of biological processes, including inflammation, hematopoiesis and overall immune response, one must inevitably look at the main pathways through which a significant number of those molecules exert their function. Janus kinase/signal transducers and activators of transcription (JAK/STATs) represent one such pathway and, recently, JAK inhibitors (JAKinibs) have shown promise in the treatment of several inflammatory diseases, including RA. This narrative review focuses on the intricate signaling pathways involved as well as on the clinical aspects and safety profiles of JAKinibs approved for the treatment of RA.

Burns have become an important public health problem in the last two decades, with just over a quarter of a million deaths annually. Major burns are accompanied by a strong inflammatory response, which will most often lead to systemic response inflammatory syndrome, followed by sepsis and finally induce multiple organ failure. The main mechanism involved in wound healing after burns is the inflammatory process, characterized by the recruitment of myeloid and T cells and by the involvement of numerous cytokines, chemokines, complement fractions, as well as various growth factors. Inflammasomes, protein-based cytosolic complexes, activated during metabolic stress or infection, play a role in modulating and improving the defense capacity of the innate immune system. Nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome has been studied predominantly and several hypotheses have been issued. Restoring the balance between the pro-inflammatory response and the anti-inflammatory activity is the key element to effective therapy in burns. Severe burns require nutritional support and pharmacotherapy not only for burn area but for different pathological complications of burn injury. In-depth research is required to find new ways to modulate the defense capacity, to prevent the complications of abnormal immune response and to treat burn injuries efficiently. Contents 1. Introduction 2. Burns and host immune response 3. The involvement of inflammasomes in burn and host immune response 4. Burns and the therapy 5. Conclusions

Chronic liver disease is a major health issue worldwide and chronic hepatitis C (CHC) is associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC). There is evidence that the hepatitis C virus (HCV) infection is correlated with immune senescence by way of immune activation and chronic inflammation, which lead to increased metabolic and cardiovascular risk, as well as progressive liver damage. Both the innate and adaptive immunity are firmly tied to the prognosis of an infection with HCV and its response to antiviral therapy. HCV is therefore associated with increased pro-inflammatory status, heightened production of cytokines, prolonged systemic inflammation, as well as increased morbidity and mortality, mainly due to the progression of hepatic fibrosis and HCC, but also secondary to cardiovascular diseases. Viral hepatic pathology is increasingly considered a disease that is no longer merely limited to the liver, but one with multiple metabolic consequences. Numerous in vitro studies, using experimental models of acute or chronic inflammation of the liver, has brought new information on immunopathological mechanisms resulting from viral infections and have highlighted the importance of involving complex structures, inflammasomes complex, in these mechanisms, in addition to the involvement of numerous proinflammatory cytokines. Beyond obtaining a sustained viral response and halting the aforementioned hepatic fibrosis, the current therapeutic "treat-to-target" strategies are presently focused on immune-mediated and metabolic disorders, to improve the quality of life and long-term prognosis of CHC patients.

The study assessed whether the increased production of interleukin-1α (IL-1α) and interleukin-1β (IL-1β), as a result of chronic hepatic inflammation, could be the expression of the negative impact on periodontal disease. The study included chronic periodontitis patients who were systemically healthy, chronic periodontitis patients suffering from chronic hepatitis C, as well as control patients, being systemically and periodontally healthy. After periodontal examination and the assessment of certain periodontal parameters, gingival crevicular fluid was collected from all participating patients. By using the enzyme-linked immunosorbent assay method, a quantitative assessment of IL-1α and IL-1β levels was possible. The immunologic results were correlated to the clinical periodontal data. The gingival fluid levels of cytokines were higher for periodontitis patients with chronic hepatitis C than for the systemically healthy periodontitis patients (1.8-fold higher for IL-1α and 2.1-fold higher for IL-1β). In addition, the gingival fluid cytokine levels were significantly higher for the periodontal patients (with/without chronic hepatitis C) than for the control group. Positive correlations were found between gingival fluid IL-1α and IL-1β levels and certain clinical periodontal parameters or the age of the viral hepatitis C diagnosis, in periodontitis patients with chronic hepatitis C. The chronic hepatic inflammation may have an important additional negative impact on the periodontal status, as both inflammatory reactions seem to be promoted by common pro-inflammatory cytokines.

In the present study, we aimed to estimate the concentrations of cytokines (interleukin 6, IL-6, tumor necrosis factor-α, TNF-α) and auto-antibodies (rheumatoid factor IgM isotype, IgM-RF, antinuclear auto-antibodies, ANA, anti–cyclic citrullinated peptide antibodies IgG isotype, IgG anti-CCP3.1, anti-cardiolipin IgG isotype, IgG anti-aCL) in serum of patients with eRA (early rheumatoid arthritis) and HCVrA (hepatitis C virus-related arthropathy) and to assess the utility of IL-6, TNF-α together with IgG anti-CCP and IgM-RF in distinguishing between patients with true eRA and HCVrA, in the idea of using them as differential immunomarkers. Serum samples were collected from 54 patients (30 diagnosed with eRA-subgroup 1 and 24 with HCVrA-subgroup 2) and from 28 healthy control persons. For the evaluation of serum concentrations of studied cytokines and auto-antibodies, we used immunoenzimatique techniques. The serum concentrations of both proinflammatory cytokines were statistically significantly higher in patients of subgroup 1 and subgroup 2, compared to the control group (p < 0.0001). Our study showed statistically significant differences of the mean concentrations only for ANA and IgG anti-CCP between subgroup 1 and subgroup 2. We also observed that IL-6 and TNF-α better correlated with auto-antibodies in subgroup 1 than in subgroup 2. In both subgroups of patients, ROC curves indicated that IL-6 and TNF-α have a higher diagnostic utility as markers of disease. In conclusion, we can say that, due to high sensitivity for diagnostic accuracy, determination of serum concentrations of IL-6 and TNF-α, possibly in combination with auto-antibodies, could be useful in the diagnosis and distinguishing between patients with true eRA and HCV patients with articular manifestation and may prove useful in the monitoring of the disease course.