Spinal cord injury (SCI) is a medical challenge that results in the formation of a glial scar preventing recovery of axonal conductivity. Cytokines and chemokines significantly affect the pathogenesis of SCI and represent important targets for therapeutic intervention. Here, dozens of cytokines and chemokines are dynamically monitored in plasma, cerebrospinal fluid, and injury site released in response to experimental SCI conducted in two rodent strains and patients undergoing surgical removal of intramedullary tumors. Dataset comprising 6,172 cytokine/chemokine values across 8 time points suggests that SCI in mammals is accompanied by a massive cytokine storm in cerebrospinal fluid, mainly driven by CXCL1, IL-6, and CCL2-5. Sub-acute phase is mostly associated with IL-2, IL-7, CCL22 and CX3CL1, whereas TNFα and IL17α permanently persists in CNS for even weeks following SCI. The effects of mogamulizumab and chemical antagonists of C-C/C-X-C chemokine receptors TAK-799, SB225002, and MK-7123 on SCI recovery in rodents are further estimated. Here blockade of CCR5 and CXCR1/2 chemokine receptors is shown beneficial for amelioration of acute SCI, whereas anti-CCR4 antibody mogamulizumab readily prevents secondary inflammation in the injured area. Summarizing, the current report claims for a novel combined time-resolved therapeutic modality in SCI treatment, which supports feasibility and motivates off-label clinical evaluation in appropriate cohorts.

OBJECTIVE:Spinal cord injury (SCI) damages an individual's sensory, motor, and autonomic functions and represents a social emergency, mostly in developed countries. Accurate and timely diagnosis of the severity of SCI must be carried out as quickly as possible to allow time for drug and therapy testing in the early stages after injury. MATERIALS AND METHODS:Male Dark Agouti (DA) rats underwent spinal cord cryoinjury at the T13 level of the spine. Under typical conditions, in vivo magnetic resonance imaging (MRI) T2 and echo-planar imaging - diffusion tensor imaging (EPI-DTI) examinations were conducted. This involved the reconstruction of nerve tracts and the measurement of the fractional anisotropy (FA) index, as well as measurements of the ratio of Hyper/Hypo intensive areas and spinal cord injury severity scores. RESULTS:Our study shows that, after cryoinjury, the FA significantly decreased in all animals. An increase in FA level, derived from EPI-DTI within 2 days after SCI, accurately predicts long-term locomotor function recovery. In rats with higher FA, recorded on day 2 after injury, complete restoration of locomotor function was observed, while at low FA values, the animals maintained stable monoplegia. CONCLUSIONS:Our results, though validating the T2 10-grade MRI scale for SCI, indicate that FA would represent the MRI technical instrument, which would better monitor the evolution of SCI and, accordingly, better objectively evaluate the impact of potentially therapeutic protocols for spinal cord traumatic injury. Despite the results achieved, significant difficulties must be overcome on the way to successful clinical implementation of the findings in humans.

In this study, we evaluated the ability of the synthetic amphipathic helical peptide (SAHP), L-37pA, which mediates pathogen recognition and innate immune responses, to treat acute respiratory distress syndrome (ARDS) accompanied by diffuse alveolar damage (DAD) and chronic pulmonary fibrosis (PF). For the modeling of ARDS/DAD, male ICR mice were used. Intrabronchial instillation (IB) of 200 µL of inflammatory agents was performed by an intravenous catheter 20 G into the left lung lobe only, leaving the right lobe unaffected. Intravenous injections (IVs) of L-37pA, dexamethasone (DEX) and physiological saline (saline) were used as therapies for ARDS/DAD. L37pA inhibited the circulating levels of inflammatory cytokines, such as IL-8, TNFα, IL1α, IL4, IL5, IL6, IL9 and IL10, by 75–95%. In all cases, the computed tomography (CT) data indicate that L-37pA reduced lung density faster to −335 ± 23 Hounsfield units (HU) on day 7 than with DEX and saline, to −105 ± 29 HU and −23 ± 11 HU, respectively. The results of functional tests showed that L-37pA treatment 6 h after ARDS/DAD initiation resulted in a more rapid improvement in the physiological respiratory lung by 30–45% functions compared with the comparison drugs. Our data suggest that synthetic amphipathic helical peptide L-37pA blocked a cytokine storm, inhibited acute and chronic pulmonary inflammation, prevented fibrosis development and improved physiological respiratory lung function in the ARDS/DAD mouse model. We concluded that a therapeutic strategy using SAHPs targeting SR-B receptors is a potential novel effective treatment for inflammation-induced ARDS, DAD and lung fibrosis of various etiologies.

Acute and subchronic toxicity of the pharmacological pair based on encapsulated Citrobacter freundii C115H methionine γ-lyase enzyme/prodrug (methiin) was studied in female ICR mice. The drug showed a weak/moderate dose-dependent hepatotoxic effect. Most of the changes in liver morphology identified were insignificant or mild deviations from the norm. Long-term use of a single therapeutic dose per mouse of 1.5 U C. freundii C115H methionine γ-lyase @ (PEG-P(Asp)70/PLL70)-PIC-some/2 mg methiin led to a slight decrease in the weight of animals without obvious signs of intoxication. A quarter of the animals in this group had no deviations from the norm in liver morphology. No nephrotoxic effect was found in any study group.

Introduction: The acute respiratory distress syndrome (ARDS), secondary to viral pneumonitis, is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019)—ongoing SARS-CoV-2 infection— reached more than 0.7 billion registered cases.Methods: Recently, we elaborated a non-surgical and reproducible method of the unilateral total diffuse alveolar damage (DAD) of the left lung in ICR mice–a publicly available imitation of the ARDS caused by SARS-CoV-2. Our data read that two C–C chemokine receptor 5 (CCR5) ligands, macrophage inflammatory proteins (MIPs) MIP-1α/CCL3 and MIP-1β/CCL4, are upregulated in this DAD model up to three orders of magnitude compared to the background level.Results: Here, we showed that a nonpeptide compound TAK-779, an antagonist of CCR5/CXCR3, readily prevents DAD in the lung with a single injection of 2.5 mg/kg. Histological analysis revealed reduced peribronchial and perivascular mononuclear infiltration in the lung and mononuclear infiltration of the wall and lumen of the alveoli in the TAK-779-treated animals. Administration of TAK-779 decreased the 3–5-fold level of serum cytokines and chemokines in animals with DAD, including CCR5 ligands MIP-1α/β, MCP-1, and CCL5. Computed tomography revealed rapid recovery of the density and volume of the affected lung in TAK-779-treated animals.Discussion: Our pre-clinical data suggest that TAK-779 is more effective than the administration of dexamethasone or the anti-IL6R therapeutic antibody tocilizumab, which brings novel therapeutic modality to TAK-779 and other CCR5 inhibitors for the treatment of virus-induced hyperinflammation syndromes, including COVID-19.

The development of CAR-T specific therapy made a revolution in modern oncology. Despite the pronounced therapeutic effects, this novel approach displayed several crucial limitations caused by the complications in pharmacokinetics and pharmacodynamics controls. The presence of the several severe medical complications of CAR-T therapy initiated a set of attempts aimed to regulate their activity in vivo. We propose to apply the barnase-barstar system to control the cytotoxic antitumor activity of CAR-T cells. To menage the regulation targeting effect of the system we propose to use barstar-modified CAR-T cells together with barnase-based molecules. Barnase was fused with designed ankyrin repeat proteins (DARPins) specific to tumor antigens HER2 (human epidermal growth factor receptor 2) The application of the system demonstrates the pronounced regulatory effects of CAR-T targeting.

Potential nonameric epitopes of CD8 + T lymphocytes were selected from the composition of structural, accessory, and nonstructural proteins of the SARS-CoV-2 virus (13 peptides) and a 15-mer epitope of CD4 + T lymphocytes, from the S-protein, based on the analysis of publications on genome-wide immunoinformatic analysis of T-cell epitopes of the virus (Wuhan strain), as well as a number of clinical studies of immunodominant epitopes among patients recovering from COVID-19 disease. The peptides were synthesized and five compositions of 6–7 peptides were included in liposomes from egg phosphatidylcholine and cholesterol (~200 nm size) obtained by extrusion. After double subcutaneous immunization of conventional mice, activation of cellular immunity was assessed by the level of cytokine synthesis by splenocytes in vitro in response to stimulation with relevant peptide compositions. Liposomal formulation exhibiting the best result in terms of the formation of specific cellular immunity in response to vaccination was selected for further experiments. Evaluation of the protective efficacy of this formulation in an infectious mouse model showed a positive trend in the frequency of occurrence of hyaline-like membranes in the lumen of the alveoli, as well as a somewhat lower severity of microcirculatory disorders. The latter circumstance can potentially help reduce the severity of the disease and prevent its adverse outcomes. A method to produce liposome preparations with peptide compositions for long-term storage is under development.

The acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019) – ongoing SARS-CoV-2 infection, reached more than 0.7 billion registered cases. Recently we elaborated non- surgical and reproducible method of unilateral total diffuse alveolar damage (DAD) of the left lung in ICR mice – a publicly available imitation of the ARDS caused by SARS-CoV-2. Our data reads that two C-C chemokine receptor 5 (CCR5) ligands – macrophage inflammatory proteins (MIP) – (MIP-1α/CCL3) and (MIP-1β/CCL4) are upregulated in this DAD model up to three orders of magnitude compared to the background level. Here we showed that a nonpeptide compound TAK- 779, antagonist of CCR5/CXCR3, readily prevents DAD of the lung with a single injection of 2.5 mg/kg. Histological analysis revealed reduced peribronchial and perivascular mononuclear infiltration in the lung, and mononuclear infiltration of the wall and lumen of the alveoli in the TAK- 779-treated animals. Administration of the TAK-779 decreased 3-5-fold level of serum cytokines and chemokines in animals with DAD, including CCR5 ligands MIP-1α/β, MCP-1 and CCL5. Computed tomography revealed rapid recovery of the density and volume of the affected lung in TAK-779- treated animals. Our pre-clinical data suggest that TAK-779 is more effective than administration of dexamethasone or anti-IL6R therapeutic antibody tocilizumab, which brings novel therapeutic modality to TAK-779 and other CCR5 inhibitors recruited in ongoing clinical studies as a potential drugs for treatment of COVID19 and similar virus-induced inflammation syndromes. Abstract summary The pathogenesis of the SARS-CoV-2 infection is tightly linked with the cytokine storm resulting in the enormous release of cytokines and chemokines. Its clinical manifestation – the acute respiratory distress syndrome (ARDS), may be caused by self-sustaining hypersensitivity reactions leading to lung collapse even after virus clearance. Here we report that two macrophage inflammatory proteins, MIP-1α/CCL3 and MIP-1β/CCL4, seem to orchestrate mononuclear infiltration into the lungs during diffuse alveolar damage (DAD) in ICR mice – our murine model of ARDS caused by SARS-CoV-2. Inhibition of the C-C chemokine receptor 5 (CCR5) – parental receptor for MIP-1α and MIP-1β, by nonpeptide antagonist TAK-779 results in significant amelioration of DAD in terms of reduced mononuclear infiltration into the lung, suppressed cytokine storm and restored physiology of affected lung according to computed tomography data. We suggest that targeted inhibition of CCR5 should be further elucidated as safe and effective approach to overcome severe viral pneumonia in humans.

OBJECTIVE:Spinal cord injury (SCI) is still one of the most challenging problems in neurosurgical practice. One of the major obstacles to neural regeneration following trauma is the formation of glial scarring and post-traumatic cysts which acts against proper growth of axons through the site of injury. Cerebrospinal fluid (CSF) delivery of bioactive agents into cystic cavities could represent a promising therapeutic strategy. In the present study, we investigated specifically the dynamics of intradural delivery of contrast medium and its relocation into post-traumatic cysts in an experimental model of spinal cord cryoinjury in rats.MATERIALS AND METHODS:32 male Sprague Dawley SPF rats were submitted to injury as previously described. Omnipaque-240 was injected either into the cisterna magna or at the level of the cauda equina. Subsequently, cerebral CT scan examinations were performed in order to check the CSF dynamics of the contrast medium.RESULTS:There was a steady accumulation of contrast medium into post-traumatic cysts as early as five minutes after injection. A dosage of 65 mg of iodine per kilogram ensured an adequate feeling of the cysts at an average of 30 minutes.CONCLUSIONS:Our data indicate that intraspinal injection of bioactive agents can easily reach the site of injury and fill post-traumatic cysts. This could represent an interesting potential therapeutic protocol for SCI.

The existing biological models of diffuse alveolar damage (DAD) in mice have many shortcomings. To offset these shortcomings, we have proposed a simple, nonsurgical, and reproducible method of unilateral total damage of the left lung in ICR mice. This model is based on the intrabronchial administration of a mixture of bacterial lipopolysaccharide (LPS) from the cell wall of S. enterica and α-galactosylceramide (inducing substances) to the left lung. Using computer tomography of the lungs with endobronchial administration of contrast material, we have been able to perform an operative intravital verification of the targeted delivery of the inducer. The model presented is characterized by more serious and homogeneous damage of the affected lung compared to the existing models of focal pneumonia; at the same time, our model is characterized by longer animal survival since the right lung remains intact. The model is also characterized by diffuse alveolar damage of the left lung, animal survival of 100%, abrupt increases in plasma levels of TNFa, INFg, and IL-6, and significant myocardial overload in the right heart. It can be used to assess the efficacy of innovative drugs for the treatment of DAD and ARDS as the clinical manifestations that are developed in patients infected with SARS-CoV-2. Morphological patterns of lungs in the noninfectious (“sterile”) model of DAD induced by LPS simultaneously with α-galactosylceramide (presented here) and in the infectious model of DAD induced by SARS-CoV-2 have been compared. The DAD model we have proposed can be widely used for studying the efficacy of candidate molecules for the treatment of infectious respiratory diseases, such as viral pneumonias of different etiology, including SARS-CoV-2.

The pathogenesis of autoimmune arthritis is a hot topic in current research. The main focus of this work was to study cytokines released in CFA-induced arthritis in ICR mice as well as the regulation of blood levels of cytokines by two peptides of the innate immunity protein Tag7 (PGLYRP1) capable of blocking the activation of the TNFR1 receptor. Arthritis was induced by local periarticular single-dose injections of 40 µL of complete Freund's adjuvant (CFA) into the left ankle joints of mice. The levels of chemokines and cytokines in plasma were measured using a Bio-Plex Pro Mouse Cytokine Kit at 3, 10, and 21 days after arthritis induction. Tag7 peptides were shown to decrease the blood levels of the pro-inflammatory cytokines IL-6, TNF, and IL-1β. Administration of peptides also decreased the levels of chemokines MGSA/CXCL1, MIP-2α/CXCL2, ENA78/CXCL5, MIG/CXCL9, IP-10/CXCL10, MCP-1/CCL2, and RANTES/CCL5. Furthermore, a decrease in the levels of cytokines IL7, G-CSF, and M-CSF was demonstrated. Addition of the studied peptides strongly affected IFN-γ concentration. We believe that a decrease in the levels of cytokine IFN-γ was associated with a therapeutic effect of Tag7 peptides manifested in alleviation of the destruction of cartilage and bone tissues in the CFA-induced arthritis.

Traumatic injury of the spinal cord is still one of the most challenging problems in the neurosurgical practice. Despite a long history of implementation of translational medicine in the field of spinal cord injury (SCI), it remains one of the most frequent causes of human disability and a critical situation for world healthcare systems. Here, we used our rat model of the of unilateral controlled SCI induced by a cryoinjury, which consistently reproduces glial scarring and posttraumatic cyst formation, and specifically evaluated histological, bioimaging and cytokine data. We propose a 10-grade scoring scale, which can objectively estimate the extent of damage of the experimental SCI according to the magnetic resonance imaging (MRI) results. It provides a homogeneous and reliable visual control of the dynamics of the posttraumatic processes, which makes it possible to clearly distinguish the extent of early damage, the formation of glial scars and the development of posttraumatic syringomyelic cysts. The concentration of cytokines and chemokines in the plasma following the experimental SCI increased up to two orders of magnitude in comparison with intact animals, suggesting that a traumatic injury of the spinal cord was accompanied by a remarkable cytokine storm. Our data suggested that the levels of IL-1α, IL-1β, TNFα, GRO/KC, G-CSF, IFNγ and IL-13 may be considered as a reliable prognostic index for SCI. Finally, we demonstrated that MRI together with plasma cytokines level directly correlated and reliably predicted the clinical outcome following SCI. The present study brings novel noninvasive and intravital methods for the evaluation of the therapeutic efficacy of SCI treatment protocols, which may be easily translated into the clinical practice.

Background: Monitoring of sanitization of cage equipment is an essential function of any laboratory animal facilities, seeking to ensure the animal health and welfare. The purpose of the current study was to develop universal scale for monitoring sanitization through detection of residual ATP for the most effective process of sanitizing components of rodents micro- and macro-environment. Methods: Sterile pens and swabs for the HY-LiTE® Luminometer Instrument were used to measure ATP concentration (RLU) on the cleaned surface samples. We have examined the elements of the microenvironment (rodent and rabbit cage, cage wire meshes, feed separating pieces, water bottles with tips, houses, tunnels, IVC cage frames, cage tops and cage wire meshes). The assessed swab area on each of the surfaces was 10×10 cm. Result: We observed, that combined washing (cleaned manually and with automatic universal washers with detergent) gives the lowest RLU values. Monitoring of the quality of sanitization of equipment and surfacescan be carried out without the use of microbiological tests. Use of pre-washing allows increasing the service life of caging equipment. We have developed an assessment scale to monitor sanitizing, which can be recommended to scientific and breeding animal facilities for monitoring sanitization cage equipments.

Search for novel regulatory protein fragments with potential functional roles is required both for understanding the immune response mechanisms and the development of targeted immunotherapy. Earlier we demonstrated that the PGLYRP1/Tag7 innate immunity protein can be regarded as an inhibitor of TNFα cytotoxic activity via the interaction with its TNF receptor 1 (TNFR1). A C-terminal peptide fragment 17.1 of the molecule is responsible for this function. In this study we have identified a minimal 8-mer region of this peptide (hereinafter – 17.1A) capable to bind to TNFR1. As a result of such interaction, the cytot o xic signals induced by this receptor are blocked. Also, this peptide demonstrates an anti-inflammatory activity in vivo in the complete Freund’s adjuvant (CFA)-induced arthritis model in laboratory mice. Peptide 17.1A is capable to reduce periarticular inflammation, inhibit the development of synovitis and exhibit a protective effect on cartilage and bone tissues. This peptide can turn out to be a promising medicinal agent for autoimmune arthritis and other diseases.

For precise ligation of a targeting and cytotoxic moiety, the use of Barnase-Barstar pair as a molecular glue is proposed for the first time. Targeting was mediated through the use of a scaffold protein DARPin_9-29 specific for the human epidermal receptor 2 (HER2) antigen that is highly expressed on some types of cancer and Barnase*Barstar native bacterial proteins interacted with each other with K-d 10(-14) M. The approach proposed consists of prelabeling a target tumor with hybrid protein DARPin-Barnase prior to administration of cytotoxic component-loaded liposomes that have Barstar covalently attached to their surface. Based on in vivo bioimaging we have proven that DARPin-based Barnase*Barstar-mediated pretargeting possesses precise tumor-targeting capability as well as antitumor activity leading to apparent tumor-growth inhibition of primary tumors and distant metastases in experimental animals. The results obtained indicate that the new system combining DARPin and Barnase*Barstar can be useful both for the drug development and for monitoring the response to treatment in vivo in preclinical studies.

Infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in many cases is accompanied by the release of a large amount of proinflammatory cytokines in an event known as “cytokine storm”, which is associated with severe coronavirus disease 2019 (COVID-19) cases and high mortality. The excessive production of proinflammatory cytokines is linked, inter alia, to the enhanced activity of receptors capable of recognizing the conservative regions of pathogens and cell debris, namely TLRs, TREM-1 and TNFR1. Here we report that peptides derived from innate immunity protein Tag7 inhibit activation of TREM-1 and TNFR1 receptors during acute inflammation. Peptides from the N-terminal fragment of Tag7 bind only to TREM-1, while peptides from the C-terminal fragment interact solely with TNFR1. Selected peptides are capable of inhibiting the production of proinflammatory cytokines both in peripheral blood mononuclear cells (PBMCs) from healthy donors and in vivo in the mouse model of acute lung injury (ALI) by diffuse alveolar damage (DAD). Treatment with peptides significantly decreases the infiltration of mononuclear cells to lungs in animals with DAD. Our findings suggest that Tag7-derived peptides might be beneficial in terms of the therapy or prevention of acute lung injury, e.g., for treating COVID-19 patients with severe pulmonary lesions.

According to the World Health Organization, every year worldwide up to 500,000 people suffer a spinal cord injury (SCI). Various animal biomodels are essential for searching for novel protocols and therapeutic approaches for SCI treatment. We have developed an original model of post-traumatic spinal cord glial scarring in rats through cryoapplication. With this method the low-temperature liquid nitrogen is used for the cryodestruction of the spinal cord tissue. Forty-five Sprague Dawley (SD) non-linear male rats of the Specific-pathogen-free (SPF) category were included in this experimental study. A Th13 unilateral hemilaminectomy was performed with dental burr using an operating microscope. A specifically designed cryogenic probe was applied to the spinal cord for one minute through the created bone defect. The animals were euthanized at different time points ranging from 1 to 60 days after cold-induced injury. Their Th12-L1 vertebrae with the injured spinal cord region were removed “en bloc” for histological examination. Our data demonstrate that cryoapplication producing a topical cooling around−20°C, caused a highly standardized transmural lesion of the spinal cord in the dorsoventral direction. The lesion had an “hour-glass” shape on histological sections. During the entire study period (days 1-60 of the post-trauma period), the necrotic processes and the development of the glial scar (lesion evolution) were contained in the surgically approached vertebral space (Th13). Unlike other known experimental methods of SCI simulation (compression, contusion, etc.), the proposed technique is characterized by minimal invasiveness, high precision, and reproducibility. Also, histological findings, lesion size, and postoperative clinical course varied only slightly between different animals. An original design of the cryoprobe used in the study played a primary role in the achieving of these results. The spinal cord lesion's detailed functional morphology is described at different time points (1–60 days) after the produced cryoinjury. Also, changes in the number of macrophages at distinct time points, neoangiogenesis and the formation of the glial scar's fibrous component, including morphodynamic characteristics of its evolution, are analyzed. The proposed method of cryoapplication for inducing reproducible glial scars could facilitate a better understanding of the self-recovery processes in the damaged spinal cord. It would be evidently helpful for finding innovative approaches to the SCI treatment.

Up to 500,000 people worldwide suffer from spinal cord injuries (SCI) annually, according to the WHO. Animal models are essential for searching novel methodological guidelines and therapeutic agents for SCI treatment. We developed an original model of posttraumatic spinal cord glial scar in rats using cryoapplication. The method is based on cryodestruction of spinal cord tissue with liquid nitrogen. Thirty six male SD linear rats of SPF category were included in this experimental study. A T13 unilateral hemilaminectomy was performed with an operating microscope, as it was extremely important not to penetrate the dura mater, and liquid nitrogen was applied into the bone defect for one minute. The animals were euthanized at various intervals ranging from 1 to 60 days after inducing cryogenic trauma, their Th12-L1 vertebrae were removed “en bloc” and the segment of the spinal cord exposed to the cryoapplicator was carefully separated for histological examination. The study results demonstrated that cryoapplication of liquid nitrogen, provoking a local temperature of approximately minus 20°C, produced a highly standardized transmural defect which extended throughout the dorsoventral arrangement of the spinal cord and had an “hour-glass” shape. During the entire study period (1-60 post-injury days), the glial scarring process and the spinal cord defect were located within the surgically approached vertebral space (Th13). Unlike other available experimental models of SCI (compression, contusion, chemical, etc.), the present option is characterized by a minimal invasiveness (the hemilaminectomy is less than 1 mm wide), high precision and consistency. Also, there was a low interanimal variability in histological lesions and dimensions of the produced defect. The original design of cryoapplicator used in the study played a major role in achieving these results. The original technique of high-precision cryoapplication for inducing consistent morphodynamic glial scarring could facilitate a better understanding of the self-recovery processes of injured spinal cord and would be helpful for proposing new platforms for the development of therapeutic strategies.

This study reviews the findings of recent experiments designed to investigate the cytokine profile after a spinal cord injury. The role played by key cytokines in eliciting the cellular response to trauma was assessed. The results of the specific immunopathogenetic interaction between the nervous and immune systems in the immediate and chronic post-traumatic periods are summarized. It was demonstrated that it is reasonable to use the step-by-step approach to the assessment of the cytokine profile after a spinal cord injury and take into account the combination of the pathogenetic and protective components in implementing the regulatory effects of individual cytokines and their integration into the regenerative processes in the injured spinal cord. This allows one to rationally organize treatment and develop novel drugs.

Investigation of interactions between a pro-inflammatory cytokine tumor necrosis factor (TNFα) and its receptor is required for the development of new treatments for autoimmune diseases associated with the adverse effects of TNFα. Earlier, we demonstrated that the innate immunity protein Tag7 (PGRP-S, PGLYRP1) can interact with the TNFα receptor, TNFR1, and block the transduction of apoptotic signals through this receptor. A complex formed between the Tag7 protein and the major heat shock protein Hsp70 can activate TNFR1 receptor and induce tumor cell death via either apoptotic or necroptotic pathway. In this study, we show that a 12-mer peptide, designated 17.1, which was derived from the Tag7 protein, can be regarded as a novel TNFα inhibitor, also is able to form a cytotoxic complex with the heat shock protein Hsp70. This finding demonstrates a new role for Hsp70 protein in the immune response. Also, this new inhibitory 17.1 peptide demonstrates an anti-inflammatory activity in the complete Freund's adjuvant (CFA)-induced autoimmune arthritis model in laboratory mice. It appears that the 17.1 peptide could potentially be used as an anti-inflammatory agent.