Dynamics Of Proinflammatory Cytokines Research Articles

CYTOKINE PROFILE RESPONSE IN PATIENTS WITH FRACTURES OF LONG BONES DURING COVID-19

Introduction: The immune system swiftly responds to the onslaught of trauma and the infectious agents it triggers. However, the mechanisms of action of the COVID-19 virus remain unidentified to date. Distinctive alterations that occur in the immune system of trauma victims with COVID-19, setting them apart from changes observed in other diseases. This underscores the specificity of traumatic disease within this patient with COVID-19.
 The study aims to assess the response of humoral immunity markers in patients with fractures of long bones and COVID-19 and to explore their role in early diagnosing infectious complications in this particular group of patients.
 Materials and methods: To accomplish the study objectives, we assembled a retrospective dataset comprising 289 cases of skeletal bone fractures treated at the Kyiv City Clinical Hospital of Emergency Medical Care from March, 2020 to February, 2021, meeting the inclusion criteria for the study. The entire dataset consisted of 289 cases of skeletal bone fractures, categorized into two groups: the main group and the control group.
 Results: On the first day of treatment, an increase in some pro-inflammatory cytokines (IL-6, IL-1β and IL-4) with a normal level of TNF-α, normal values of IFN-γ, IFN-α and a sharp decrease in the anti-inflammatory cytokine IL was observed among the patients of the main group -10. On the third day of the treatment, there was a significant increase in all pro-inflammatory cytokines (IL-6, IL-1β, IL-4 and TNF-α), both types of interferons, and an even sharper decrease in the anti-inflammatory cytokine IL-10. On the tenth day, the growth in the level of pro-inflammatory cytokines was noted, among which the level of TNF-α was the leader, a subnormal level of interferons and anti-inflammatory interleukin 10 was observed. Conclusions: The dynamics of pro-inflammatory cytokines in patients with long bone fractures against the background of COVID-19 tended to increase and had a maximum level on the third day of treatment. Anti-inflammatory cytokines demonstrate a tendency to depression and reache the reference value only on the 10th day of the study.

Pro-inflammatory cytokines are modified during the multiplication of Trypanosoma cruzi within the placental chorionic villi and are associated with the level of infection via the signaling pathway NF-κB.

Congenital Trypanosoma cruzi (T. cruzi) infection has been associated with changes in the levels of TNF-α and IFN-γ during the pregnancy. Therefore, we propose to study the participation and dynamics of proinflammatory cytokines in the infection process of placental explants infected by T. cruzi in vitro. Chorionic villous explants (CVE) obtained of human term placentas (n=8) from normal pregnancies were cultured with 105 trypomastigotes/mL of Tulahuen strain DTU VI for 0, 2, 4, 16, 24, 48 and 72h. Explants were treated with sulfasalazine (SULF) (5mM) and N-acetyl-cysteine (NAC) (15mM), as inhibitors molecules of NF-κB pathway, or LPS (1μg/mL) for 24 and 72h p.i. Motile trypomastigotes were counted in culture supernatants. Immunohistochemistry and ELISA for TNF-α, IFN-γ, IL-1β, IL-4, and IL-10 were performed in CVE and culture supernatants respectively. The parasite load was measured by RT-qPCR. T. cruzi invades the chorionic villi from 4h p.i. increasing significantly its DNA at 48 and 72h p.i. of culture (parasite multiplication phase). They were detected in stromal cells, which was related to elevation of TNF-α, IL-1β, IFN-γ, and IL-10. The inhibition of NF-κB activity in the explants decreased the production of the analyzed cytokines, showing elevated levels of T. cruzi DNA during the multiplication phase of the parasite. Placental tissue modifies the secretion of pro-inflammatory cytokines during the phase of parasite multiplication, but not during the invasion phase, which in turns modifies the level of infection via the signaling pathway NF-κB.

Indicators of immunological response to non-drug therapy of chronic adenoiditis

The aim of our work was to study individual indices of immune response in children with chronic adenoiditis and evaluate their dynamics following low-frequency ultrasonic cavitation combined with photochromotherapy included into the treatment regimen. The study involved 104 patients 3 to 15 years old, divided into three groups: the 1st control group (n = 34) received standard treatment for 7 days; 2nd group (n = 37) received a supplementary low-frequency ultrasonic cavitation irrigation of pharyngeal tonsil combined with photochromotherapy on lymphoid tissue of the pharyngeal tonsil for 7 days; the 3rd group (n = 33) received only low-frequency ultrasonic cavitation irrigation treatment. Comparative estimation of clinical and immunological indicators (sIgA, IL-1, IL-6, IL-8, IL-10, TNF) was performed prior to the therapy (day 0) and on the 7th day from the start of treatment. Before therapy, a decrease in the content of sIgA, IgA was revealed in all groups. In the second group, there was a statistically significant increase in the level of IgA after treatment, which suggests activation of local immunity factors. The dynamics of proinflammatory cytokines (IL-6, IL- 10) also indicates effectiveness of the drug treatment by reducing manifestations of the tissue immunological reactivity in pharyngeal tonsil. An increased number of anti-inflammatory IL-8 and IL- 10 cytokines could be considered a compensatory response to decreased level of proi-inflammatory cytokines.
 As a result, the inclusion of low-frequency ultrasonic cavitation in combination with photochromotherapy into the complex treatment for chronic adenoiditis thus stabilizing the course of immune response.

Cytokine balance as a diagnostic marker of inflammation in experimental purulent lesions of soft tissues

Inflammatory process is at the heart of artificial (artificial) purulent-inflammatory diseases of soft tissues (APDST), which may lead to the development of phlegmon and abscesses at the site of invasion within a three-day period. The study of the cytokine status of rats with APDST allows us to evaluate the dynamics of inflammation markers and assess the peculiarities of the pathological course in artificial model of inflammation. The experiment was carried out on 126 white Wistar rats divided into 3 groups: (1) the main group (n = 57), where the laboratory model of APDST was used; (2) a comparison group (n = 58), in which the rats were injected with a mixture of opportunistic bacterial strains isolated from pure cultures of human oral fluid, i.e., S. epidermidis, S. mitis, S. salivarius at the titer of 9lg (CFU) per 1 ml injected together with a mixture of 2.5% hydrocortisone acetate emulsion (20 mg per 100 g of animal body weight), and dexamethasone solution at the dose of 0.5 mg; (3) control group (n = 11), where the animals were injected with 0.9% sodium chloride solution in a volume of 0.3 ml, together with a mixture of 2.5% hydrocortisone acetate emulsion at the rate of 20 mg per 100 g of body weight, and dexamethasone solution at the dose of 0.5 mg. Blood cells were studied using the Mindray DC-2800 Vet Auto Hematology Analyzer automated rat blood test system. The dynamics of pro-inflammatory cytokines: tumor necrosis factor (TNF), interleukin-1β (IL-1β), interleukin-6 (IL-6), antiinflammatory cytokines: interleukin-4 (IL-4), interleukin-10 (IL-10) was assessed by enzyme immunoassay. To predict the course of inflammation towards complications, or resolution of the inflammatory process, the ratio of pro-inflammatory to anti-inflammatory cytokines was used, with normal ratio considered an estimated average of the cytokine ratio for the control group. When analyzing results of this experimental study, the nature of cellular inflammatory response was assessed in dynamics, and its relationship with inflammation markers was determined. All animals of the main group developed soft tissue phlegmon within 3 to 7 days from the beginning of the experiment, and their mortality rate was 100%. In comparison group, the abscesses developed in 82.8% of cases on the day 12 to 15 from the start of the experiment, without any deaths observed. The ratio of pro- and anti-inflammatory cytokines in the main group increased 8-fold already by the end of the 1st day, the comparison group was characterized by the absence of significant differences from the control group. The highest levels of pro-inflammatory cytokines were recorded in the main experimental group on the days 12 to 15.

The features of the course of virus-associated acute lung injury in mice with induced immunosuppression

BACKGROUND: Among all groups of patients with virus-associated acute lung injury with influenza infection, the most severe course is observed in patients with immunosuppression. In this case, despite the studied mechanism of the course of combined pathology, the question of therapy in this group of patients remains unclear.
 AIM: To study the features of the course of acute lung injury in influenza infection with secondary immunosuppression in an experiment for the possibility of searching for experimental therapy for this combined pathology.
 MATERIALS AND METHODS: The study was performed on 115 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral acute lung injury. Experimental immunosuppression was reproduced by administration of methotrexate (1.25 mg/kg intraperitoneally, once every 3 days during 3 weeks before infection). During the experiment, mortality, blood oxygen saturation, the concentration of pro-inflammatory cytokines in the lungs, and the severity of lung injury were measured.
 RESULTS: The presence of experimental immunosuppression led to an exacerbation of acute lung injury in infected animals in terms of mortality and lung damage. Changes in the dynamics of proinflammatory cytokines (TNF-, IL-6, IL-1) in the lungs were observed during acute lung injury. Retarded recovery of the lungs functional activity was noted.
 CONCLUSIONS: The experimental immunosuppression contributed to the exacerbation of acute lung injury and to an increase in the duration of the pathology. These changes could be associated with an altered process of elimination of the pathogen. The reproduced model of combined pathology was used for searching a therapy for these complications.

Young Investigator: Dynamics of Proinflammatory Cytokines in Patients With Crohnʼs Disease Who Received Combined Therapy With Mesenchymal Stromal Cells and Azathioprine

Young Investigator: Dynamics of Proinflammatory Cytokines in Patients With Crohnʼs Disease Who Received Combined Therapy With Mesenchymal Stromal Cells and Azathioprine

Profiles of pro-inflammatory cytokines in allogenic stem cell transplantation with post-transplant cyclophosphamide

Large number of studies was published about predictive value of cytokines for graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Recently, there has been a growing interest in GVHD prophylaxis with post-transplant cyclophosphamide (PTCy). Clinical data on the dynamics of proinflammatory cytokines with this prophylaxis is lacking. In this study, we have measured the levels of IL-17, IL-6, IL-8, IFN-γ and TNF-α in plasma on days −7, 0, +7, +14 and after engraftment in 20 patients with acute GVHD and 40 matched control patients with PTCy-based prophylaxis. Low levels of IL-8 (p=0.04) on day +7 and IFN-γ (p=0.03) after engraftment were associated with grade II-IV acute GVHD. The same pattern was observed for severe acute GVHD. Low IFN-γ after engraftment was also associated with increased non-relapse mortality (p=0.014). No impact of cytokine levels on overall survival and relapse incidence was observed (p>0.05). In conclusion, the dynamics of IL-8 and IFN-γ in GVHD patients after PTCy was different from previously reported after conventional prophylaxis.

Early Dynamics of Interleukin-6 in Cerebrospinal Fluid after Aneurysmal Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a severe condition associated with high mortality. Early brain injury (EBI) plays an important role in the pathophysiology of SAH, and inflammation is a major contributor to EBI. Inflammation is a widely studied topic in both experimental and clinical conditions; however, just a few clinical studies have focused primarily on the early inflammatory response after SAH, and detailed information about the association between the dynamics of early inflammatory response with main clinical characteristics is lacking. This study analyzes the early dynamics of inflammatory response after SAH and evaluates the possible associations between the markers of early inflammatory response and main clinical characteristics. A total of 47 patients with a diagnosis of aneurysmal SAH within the last 24 hours were enrolled in the study. All treatments, including treatment of aneurysm (surgery/coiling) and implantation of a drainage system (external ventricular drainage/lumbar catheter), were conducted in the same way as in other patients with this diagnosis. Blood and cerebrospinal fluid (CSF) samples were collected three times a day for 4 days. The dynamics of proinflammatory cytokines were assessed, and associations between levels of the proinflammatory cytokines interleukin (IL)-6, IL-1β, or tumor necrosis factor (TNF)α and main clinical characteristics were evaluated using linear mixed-effect models. The CSF levels of IL-6 were massively increased initially after SAH (up to 72 hours) with an additional increase in later phases (after 72 hours), but there was high variability in IL-6 levels. A significant association was noted between the Glasgow Outcome Scale score and both overall levels of IL-6 (p = 0.0095) and their dynamics (p = 0.0208); the effect of the Hunt and Hess scale was borderline (p = 0.0887). No association was found between IL-6 levels and Fisher grade, modality of treatment (surgery, coiling, no treatment), and later development of cerebral vasospasm. Plasmatic levels of IL-6 increased slightly, but no significant association was found. The levels of IL-1β and TNFα were within the physiologic range in both CSF and plasma. Early dynamics of IL-6 in CSF are associated with a patient́s outcome. But it is difficult to use IL-6 alone for outcome prediction due to its high variability. The question is whether the dynamics of IL-6 could be used in combination with other early markers associated with brain injury. More detailed research is required to answer this question.

Dynamics of proinflammatory cytokines at phlegmons of the maxillofacial area

Dynamics of proinflammatory cytokines at phlegmons of the maxillofacial area