Study of various therapeutic strategies for the treatment of rapidly progressive periodontitis in experimental models.

Rapidly progressive periodontitis is a serious disease that leads to rapid degradation of periodontal tissues and can lead to tooth loss at a relatively young age. The purpose of this article is to study the effectiveness of various modern methods in the treatment of this disease on an experimental model. A model of the studied pathology was created - a rat with a destroyed circular ligament of the tooth and a ligature applied to the base of the teeth. 5 study groups were formed, where various treatment methods were used: the appointment of soft food, the combination of intramuscular administration of vitamin C and prednisolone, the combination of tocilizumab and dexamethasone, and the combination of photodynamic therapy and tocilizumab. Histological material was taken from experimental animals and evaluated. The best results were noted in the group of photodynamic therapy and tocilizumab, where there was a better histological picture with minimal signs of the inflammatory process and satisfactory indicators of clinical dynamics, this approach showed high efficiency in resolving inflammation in the area of the affected foci. The 2nd place was taken by the combination of tocilizumab and dexamethasone, in this group, accelerated positive dynamics were noted compared to other groups, but the results of histological examination were worse than in group 1. In 3rd place - the combination of ascorbic acid with dexamethasone and the appointment of soft food, where there were almost no differences in terms of histological results and clinical picture compared to the control group. The combination of tocilizumab with photodynamic therapy is promising in the treatment of patients with rapidly progressive periodontitis, but additional human studies are required to include this type of treatment in clinical guidelines.

Neurological Complications of Biological Treatment of Psoriasis.

In the available literature, little attention has been paid to the assessment of psoriasis and the biological therapy used for it and the nervous system. The purpose of this article is to discuss the relationship between psoriasis and the nervous system as well as to analyze the mechanisms that lead to neurological complications during anticytokine therapies in psoriasis. However, this connection requires further analysis. The use of biological drugs in psoriasis, although it yields positive therapeutic results, is not without numerous side effects. Serious neurological side effects of the therapy are most often visible with the use of anti-TNF-alpha, which is why patients should be monitored for their potential occurrence. Early detection of complications and rapid discontinuation of treatment with the drug may potentially increase the patient's chances of a full recovery or improvement of his/her neurological condition. It also seems reasonable that, in the case of complications occurring during anti-TNF-alpha therapy, some of the drugs from other groups should be included in the therapy.

Novel Anti-Cytokine Strategies for Prevention and Treatment of Respiratory Allergic Diseases.

Asthma is a heterogeneous inflammatory disease characterized by airflow obstruction, wheezing, eosinophilia and neutrophilia of the airways. Identification of distinct inflammatory patterns characterizing asthma endotypes led to the development of novel therapeutic approaches. Cytokine or cytokine receptor targeting by therapeutic antibodies, such as anti-IL-4 and anti-IL-5, is now approved for severe asthma treatment. However, the complexity of cytokine networks in asthma should not be underestimated. Inhibition of one pro-inflammatory cytokine may lead to perturbed expression of another pro-inflammatory cytokine. Without understanding of the underlying mechanisms and defining the molecular predictors it may be difficult to control cytokine release that accompanies certain disease manifestations. Accumulating evidence suggests that in some cases a combined pharmacological inhibition of pathogenic cytokines, such as simultaneous blockade of IL-4 and IL-13 signaling, or blockade of upstream cytokines, such as TSLP, are more effective than single cytokine targeting. IL-6 and TNF are the important inflammatory mediators in the pathogenesis of asthma. Preliminary data suggests that combined pharmacological inhibition of TNF and IL-6 during asthma may be more efficient as compared to individual neutralization of these cytokines. Here we summarize recent findings in the field of anti-cytokine therapy of asthma and discuss immunological mechanisms by which simultaneous targeting of multiple cytokines as opposed to targeting of a single cytokine may improve disease outcomes.

[Pro-inflammatory cytokines in chronic cardiac failure: state of problem].

Systemic inflammation is characterized by the induction of pro-inflammatory cytokines, the increased level of which in the blood of patients with chronic heart failure (CHF) correlates with unfavorable clinical outcomes. However, it is unclear whether pro-inflammatory cytokines are the cause or the consequence of the disease progression. CHF with preserved ejection fraction and CHF with reduced ejection fraction demonstrate different inflammatory features, which suggests different degrees of pro-inflammatory pathway activation. The review deals with participation of pro-inflammatory cytokines in pathophysiological processes of CHF development, emphasizing the role of interleukin-6 activation and the effects of accompanying diseases on the course of systemic inflammation. The search for new approaches to prevention and therapy of CHF remains actual. The review presents the results of clinical trials of targeted anti-cytokine therapy which have revealed difficulties in controlling inflammation under the conditions of CHF. Identification of specific pro-inflammatory pathways in CHF pathogenesis will allow one to control inflammatory cascades, thus providing a prospective therapeutic strategy.

Clinical Effectiveness of a Combination of Black Elder Berries, Violet Herb, and Calendula Flowers in Chronic Obstructive Pulmonary Disease: The Results of a Double-Blinded Placebo-Controlled Study.

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease, in which systemic inflammation plays a key role. This 6-month randomized double-blinded placebo-controlled study evaluates the possible effect of natural preparation Inflaminat on clinical symptoms of COPD, indicators of respiratory function, and exacerbation frequency in 60 patients with moderate severity of COPD. Inflaminat is a combination of natural ingredients black elder (Sambucus nigra L.) berries, violet (Viola tricolor L.) herb, and calendula (Calendula officinalis L.) flowers. The preparation has been previously demonstrated to possess anticytokine and anti-inflammatory effects in experimental studies. In present study, COPD dynamics were evaluated by means of BCSS (Breathlessness, Cough, and Sputum Scale) and spirometry tests. It was shown that 6-months Inflaminat administration led to significant decrease of BCSS points from 3.0 ± 0.6 to 1.9 ± 0.7, (p = 0.002) as well as significant increase of FEV1 from 66 ± 18% to 73 ± 17%, (p = 0.042); there were no beneficial dynamics in placebo group. Side effects associated with preparation administration were not identified. The results of the study suggest that Inflaminat may be employed in treatment of patients with moderate severity of COPD, since it has a positive effect on COPD symptoms according BCSS and indicators of respiratory function FEV1.

Antibody blockade of IL-17 family cytokines in immunity to acute murine oral mucosal candidiasis.

Antibodies targeting IL-17A or its receptor, IL-17RA, are approved to treat psoriasis and are being evaluated for other autoimmune conditions. Conversely, IL-17 signaling is critical for immunity to opportunistic mucosal infections caused by the commensal fungus Candida albicans, as mice and humans lacking the IL-17R experience chronic mucosal candidiasis. IL-17A, IL-17F, and IL-17AF bind the IL-17RA-IL-17RC heterodimeric complex and deliver qualitatively similar signals through the adaptor Act1. Here, we used a mouse model of acute oropharyngeal candidiasis to assess the impact of blocking IL-17 family cytokines compared with specific IL-17 cytokine gene knockout mice. Anti-IL-17A antibodies, which neutralize IL-17A and IL-17AF, caused elevated oral fungal loads, whereas anti-IL-17AF and anti-IL-17F antibodies did not. Notably, there was a cooperative effect of blocking IL-17A, IL-17AF, and IL-17F together. Termination of anti-IL-17A treatment was associated with rapid C. albicans clearance. IL-17F-deficient mice were fully resistant to oropharyngeal candidiasis, consistent with antibody blockade. However, IL-17A-deficient mice had lower fungal burdens than anti-IL-17A-treated mice. Act1-deficient mice were much more susceptible to oropharyngeal candidiasis than anti-IL-17A antibody-treated mice, yet anti-IL-17A and anti-IL-17RA treatment caused equivalent susceptibilities. Based on microarray analyses of the oral mucosa during infection, only a limited number of genes were associated with oropharyngeal candidiasis susceptibility. In sum, we conclude that IL-17A is the main cytokine mediator of immunity in murine oropharyngeal candidiasis, but a cooperative relationship among IL-17A, IL-17AF, and IL-17F exists in vivo. Susceptibility displays the following hierarchy: IL-17RA- or Act1-deficiency > anti-IL-17A + anti-IL-17F antibodies > anti-IL-17A or anti-IL-17RA antibodies > IL-17A deficiency.