Recurrent assessment of lymphocyte subsets in 32 patients with multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Lymphopenia is a hallmark of multisystem inflammatory syndrome in children (MIS-C). We aimed to characterize lymphocyte subsets' shifts and their correlations with other severity markers of MIS-C. METHODS: In this prospective cross-sectional study, we performed peripheral lymphocyte phenotyping in 32 patients with MIS-C. We analyzed lymphocyte subsets at three time points of the disease: the acute (A), convalescent (B), and recovery (C) phases. Based on age-normalized lymphocyte counts, we distinguished two groups of patients: "the mild" (higher lymphocyte counts) and "the severe" (lower lymphocyte counts). In addition, we examined differences between these groups regarding other severity markers. RESULTS: In phase A, 84% of children had lymphopenia. Decreased absolute counts of CD3, CD4, and CD8 cells were observed in, respectively, 88%, 72%, and 84% of patients. The natural killer cells were decreased in 63% and CD19 in 59% of children. "The severe" group had significantly higher procalcitonin and troponin I levels and lower platelets and albumin. Moreover, "the severe" group had hypotension more frequently (73% vs. 20%, p = .008). In phase B, all lymphocyte counts increased, and 32% of children had lymphocytosis. The increase of CD3, CD4, and CD8 counts correlated with some laboratory severity markers (hemoglobin, procalcitonin, D-dimer, lactate dehydrogenase, N-terminal prohormone of brain natriuretic peptide, albumin), but not with steroid use. In phase C, most children had normal lymphocyte counts. CONCLUSIONS: Substantial shifts in lymphocyte counts during MIS-C apply most to T lymphocytes and correlate with the disease severity markers, particularly hypotension prevalence. A proportion of children with MIS-C develops transient lymphocytosis during convalescence.

Acute Systemic Inflammatory Response Alters Transcription Profile of Genes Related to Immune Response and Ca2+ Homeostasis in Hippocampus; Relevance to Neurodegenerative Disorders.

Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer's disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 gene encoding calgranulin A was activated (FC = 2.9). Gene ontology enrichment analysis demonstrated the alteration of gene expression related mostly to the immune-response including the gene Lcn2 for Lipocalin 2 (FC = 237.8), involved in glia neurotoxicity. The expression of genes coding proteins involved in epigenetic regulation, histone deacetylases (Hdac4,5,8,9,11) and bromo- and extraterminal domain protein Brd3 were downregulated; however, Brd2 was found to be upregulated. Remarkably, the significant increase in expression of Lcn2, S100a8, S100a9 and also Saa3 and Ch25h, was found in AD brains suggesting that early changes of immune-response genes evoked by mild SIR could be crucial in AD pathogenesis.

Assessment of systemic inflammatory response after total extraperitoneal repair and Lichtenstein repair for inguinal hernia.

PURPOSE: The aim of the study was assessment of the systemic inflammatory response (SIR) intensity by measuring the blood serum levels of high sensitivity C-reactive protein (hsCRP), Interleukin-6 (IL-6) and Total Leukocyte Counts of patients. The estimations were done before and after the patient underwent either open Lichtenstein or endoscopic TEP inguinal hernia repair. This is a prospective observational type of study. METHODS: Sixty patients with a diagnosis of unilateral uncomplicated inguinal hernia were included in the study. Patients were divided into two groups. In the first group, endoscopic total extraperitoneal repair (TEP) was done, while the other group underwent Lichtenstein repair. The patient selection was random. Serum markers for SIR were measured prior to and 24 h post-surgery. RESULTS: Total extraperitoneal repair (TEP) and open Lichtenstein inguinal hernia repair both cause a significant Systemic Inflammatory Response in the body. The rise in serum markers for SIR post-surgery was statistically significant in both the groups. The rise in serum hsCRP and IL-6 concentrations was observed to be equivocal among the two groups. Statistically significant difference was observed in serum TLC rise: Lichtenstein repair group having a higher value. CONCLUSION: Both, open and endoscopic surgical techniques incite a systemic inflammatory response in the body. However, it cannot be conclusively stated that TEP is associated with lesser SIR compared to the Lichtenstein repair on the basis of this study.

The use of imaging technology in the assessment of the fetal inflammatory response syndrome-imaging of the fetal thymus.

The fetal inflammatory response syndrome (FIRS) describes a state of extensive fetal multi organ involvement during chorioamnionitis, and is associated with grave implications on perinatal outcome. The syndrome has been linked to the preterm parturition syndrome and is associated with inflammation/infection processes in most of the fetal organs. The fetal thymus, a major organ in the developing immune system involutes during severe neonatal disease and has been shown to be smaller in fetuses with FIRS. Various methods for imaging of the fetal thymus and measurement are described. Currently the only method to diagnose FIRS prenatally is through amniocentesis. We suggest that women who are admitted with preterm labor with intact membranes and those with PPROM should have a detailed sonographic examination of the fetal thymus as a surrogate marker of fetal involvement in intrauterine infection/inflammation processes.

[Immuno-nutrition in intensive care and emergency surgery].

The aim of the study is the improvement of nutritional support by immuno nutrition of patients, who are in critical conditions. The data on the impact of immuno active mixes (on the example of the mixture of Impact) on the immune and inflammatory response. In this, the number of postoperative infectious complications have been reliably decreased, the duration of the stay in the Department of R&IT and the hospital has been dicresed in whole, the cost of treatment in comparison with the use of standard schemes of patients with surgical and oncological profile has been significantly reduced.

Circulating cytokine levels in acute pancreatitis-model of SIRS/CARS can help in the clinical assessment of disease severity.

The aim of our study was to evaluate the pro- and anti-inflammatory cytokine response during acute pancreatitis and its predictive value on severity of disease. A hospital-based prospective clinical study was conducted. Twenty patients with acute pancreatitis were enrolled during a 12-month period. Plasma concentrations of TNF-α, IL-1ß, IL-6, and IL-10 were determined at days 1, 2, 3, 6, and 9. The patient population was analyzed by type of acute pancreatitis. Severity was defined according to the Atlanta criteria for assessing severity of acute pancreatitis. Clinical variables were recorded to patients classified in one of two groups: severe acute pancreatitis (SAP group) and mild acute pancreatitis (MILD group). Patients with SAP had significantly higher average levels of IL-6 compared to the MILD group patients (539.2 pg/L vs. 23.4 pg/L, p < 0.0001). Also, the values of IL-10 were significantly higher in patients with SAP (242.4 pg/L vs. 8.1 pg/L, p = 0.003). The values of TNF-α were not significantly different in both groups. The value of IL-6 and IL-10 showed a positive correlation (r = 0.7964, p < 0.0001). Although a relatively small sample of patients was used, we can conclude that the determination of the value of IL-6 and IL-10 can help in the clinical assessment of disease severity.

Clinical and immunologic assessment of sepsis and the systemic inflammatory response syndrome in cats.

OBJECTIVE: To compare clinical findings and inflammatory mediator production among cats with sepsis, cats with noninfectious systemic inflammatory response syndrome (SIRS), and healthy cats. DESIGN: Case-control study. ANIMALS: Cats with sepsis (n = 16) or SIRS (19) and 8 healthy control cats. PROCEDURES: Clinical variables were recorded for each cat, and plasma tumor necrosis factor (TNF) and interleukin (IL)-1ß activities and IL-6 and CXC chemokine ligand (CXCL)-8 concentrations were determined at initial evaluation. RESULTS: Clinicopathologic abnormalities associated with sepsis in cats included a high band neutrophil percentage, eosinopenia, hyponatremia, hypochloremia, hypoalbuminemia, hypocalcemia, and hyperbilirubinemia. When the sepsis and SIRS groups were compared, the only significant differences in the CBC and plasma biochemical findings were band neutrophil percentage and albumin concentration. Cats with sepsis had significantly greater plasma TNF activity than did healthy cats and were more likely to have detectable concentrations of IL-6 than were cats with SIRS or healthy cats. Plasma IL-1ß activity did not differ among groups, and CXCL-8 was not detectable in most (32/43) cats. Mortality rate was not significantly greater for cats with sepsis (7/16) than for cats with SIRS (5/19). Plasma IL-1ß activity and IL-6 and chloride concentrations were the only variables correlated with nonsurvival in the sepsis group. CONCLUSIONS AND CLINICAL RELEVANCE: Cats with sepsis may have various clinicopathologic abnormalities but are more likely to have a high band neutrophil percentage and hypoalbuminemia than cats with noninfectious SIRS. Plasma interleukin-1ß activity and plasma IL-6 and chloride concentrations may be useful prognostic biomarkers for septic cats.

Assessment of the clinical course with inflammatory parameters.

Inflammatory changes after trauma depend on the severity and the distribution of the injury and can be modified by the medical treatment. They precede the development of organ dysfunction and may be used for monitoring purposes. Among these, pro-inflammatory cytokines appear to be the most reliable parameters.

[Clinical assessment of immune parameters at surgical patients with syndrome of systemic inflammatory reaction].

Results of immunological examination of 423 patients with syndrome of systemic inflammatory reaction of different ethiology (mediastinitis--78 patients, peritonitis--85, severe acute pancreatitis--91, trauma of thorax and abdomen complicated with massive hemorrhage--111, severe burn trauma--40 patients) are analyzed. For complex and objective assessment of immune reaction the system of scores has been developed. This scale permitted to detect the immune disorders, to diagnose the degree of immune insufficiency at early stages of disease, to predict the purulent complications and to start timely immune therapy.

Assessment of inflammatory response and sequestration of blood iron transferrin complexes in a rat model of lung injury resulting from exposure to low-frequency shock waves.

OBJECTIVE: Impact of air blast overpressure waves (OPW), or shock wave, with the body wall or body armor produces two types of energy waves: high-frequency low-amplitude stress waves and long-duration low-frequency share waves. These types of energy waves are characterized by different mechanisms of primary tissue injury that mostly affect lung. Systemic inflammation and resultant acute respiratory distress syndrome are known major secondary causative agents of delayed multiple organ failure and subsequent death after OPW exposure. However, association of each pattern of the blast OPW-produced energy waves with postexposure inflammatory events has not yet been delineated. The objectives of the present research were a) establishment of a rat model for assessment of the inflammatory response following lung injury produced by exposure to medium-amplitude (approximately 120 kPa) low-frequency (260+/-5 Hz) OPWs; and b) assessment of the dynamics of alteration in polymorphonuclear leukocyte counts and expression of CD11b adhesion molecules on the surface of polymorphonuclear leukocytes and status of iron-transferrin complexes in peripheral blood after OPW exposure. DESIGN: This study focused on the OPW effects at different time periods, using a sequential approach to postexposure events. Lung injury in rat was induced by OPW generated in a laboratory shock tube. Animals were exposed to OPW (at peak overpressure of 118+/-7 kPa) that produced "moderate" lung injury. SETTING: Military research institute. SUBJECTS: Twenty-seven CVF Sprague-Dawley rats were subjected to OPW exposures, and 17 sham-treated animals were used as control. INTERVENTIONS: Lung tissue and blood samples were collected at 1, 3, 6, 12, and 24 hrs following OPW exposures and compared with samples collected from nonexposed animals. MEASUREMENTS AND MAIN RESULTS: OPW-induced lung injury caused a 2.7-fold increase in the number of circulatory polymorphonuclear leukocytes as early as 1 hr postexposure, which is indicative of mobilization of the pool of marginated polymorphonuclear leukocytes into the free circulation. Polymorphonuclear leukocyte counts increased through the following 3- and 6-hr periods, when they were, respectively, 5-fold and 3.5-fold higher than in controls. These effects were accompanied by a pronounced expression of CD11b in polymorphonuclear leukocytes and tissue sequestration of blood iron-transferrin complexes during the entire 24-hr period of observations. The increase in circulatory polymorphonuclear leukocytes was accompanied by a decrease in iron-transferrin complex concentrations that apparently reflected implication of blood plasma iron in the inflammatory cell response to OPW-induced injury. CONCLUSIONS: The observed dynamics in polymorphonuclear leukocyte alterations in peripheral blood after OPW exposure were similar to those found recently in clinical observations of nonpenetrating injury and in animal models of infectious insults. Therefore, our data suggest that the main pattern of proinflammatory alterations in the rat model of lung injury induced by exposure to long-duration shock wave is similar to patterns that are characteristic of major trauma. The data further suggest that the expression of polymorphonuclear leukocyte CD11b and the response of iron-transferrin complex can be considered as potential surrogate markers in blood for systemic alterations following OPW-induced injury and, therefore, warrant further investigation in a human pilot study.

Avances y promesas en la inmunoterapia de sepsis neonatal / Advances and promises in immunotherpy for neonatal sepsis

La sepsis neonatal es una infección sistémica en el primer mes de vida que, según su gravedad, presenta las 4 fases del síndrome de respuesta inflamatoria sistémica (SRIS) que caracteriza a esta enfermedad en los adultos. El uso de antibióticos sigue siendo el pilar en su tratamiento; sin embargo, la morbi-letalidad de la sepsis neonatal no ha disminuido significativamente y la aparición de cepas resistentes es alarmante, lo cual plantea la necesidad de alternativas terapéuticas. En esta búsqueda, se pretende regular la respuesta inflamatoria a la infección a través de 3 grandes grupos de citocinas: interleucinas, interferones y los factores de crecimiento, algunas de las cuales se comportan como pro-inflamatorias, y otras como anti-inflamatorias al neutralizar, bloquear o inhibir a las pro-inflamatorias. Hasta ahora, los 2 mayores avances en la terapia auxiliar de sepsis neonatales son la inmunoglobulina para uso intravenoso (IgIV), que tiene su principal indicación en los neonatos prematuros y de bajo peso, y los factores estimulantes de colonias de granulocitos y de macrófagos (G-CSF y GM-CSF), indicados en neonatos pretérmino o a término con neutropenia por sepsis. Una actitud de extrema reserva entre muchos médicos ha postergado de manera poco justificable su aplicación clínica. En fases preliminares de investigación se encuentran los antagonistas naturales de la endotoxina bacteriana, como la BPI, proteína producida por los granulocitos, y las inmunoadhesinas, moléculas híbridas de inmunoglubulina y un receptor específico que bloquean la unión de citocinas pro-inflamatorias con sus receptores celulares, modulando así la respuesta inflamatoria a la infección

Inflammatory response to cardiopulmonary bypass.

This article reviews the roles of the contact and complement systems and of neutrophils and monocytes in the inflammatory response to cardiopulmonary bypass and open heart operation. These blood proteins and cells, together with other blood elements, produce the vasoactive and cytotoxic substances and microemboli that cause the morbidity associated with cardiopulmonary bypass and open heart operation.