International Journal of Inflammation最新文献

Experimental work of the last two decades has revealed the general steps of the wound healing process. This complex network has been organized in three sequential and overlapping steps. The first step of the inflammatory phase is an immediate response to injury; primary sensory neurons sense injury and send danger signals to the brain, to stop bleeding and start inflammation. The following target of the inflammatory phase, led by the peripheral blood mononuclear cells, is to eliminate the pathogens and clean the wound. Once this is completed, the inflammatory phase is resolved and homeostasis is restored. The aim of the proliferative phase, the second phase, is to repair wound damage and begin tissue remodeling. Fibroplasia, reepithelialization, angiogenesis, and peripheral nerve repair are the central actions of this phase. Lastly, the objective of the final phase is to complete tissue remodeling and restore skin integrity. This review provides present day information regarding the status of the participant cells, extracellular matrix, cytokines, chemokines, and growth factors, as well as their interactions with the microenvironment during the wound healing process.

On the model of the systemic inflammatory response (SIRS), induced by lipopolysaccharide (LPS), the morphological and functional changes in the thymus and spleen and the subpopulation composition of peripheral blood lymphocytes of rats differing in resistance to hypoxia were studied. It was demonstrated that the level of endotoxin in blood serum after 3 hours of LPS administration in susceptible-to-hypoxia rats was 64 times higher than in the control group, while in tolerant-to-hypoxia animals it was only 8 times higher in 6 hours. After 24 hours of LPS injection, only in susceptible-to-hypoxia rats did the level of C-reactive protein in blood serum increase. There is a difference in the dynamics of morphological changes of lymphoid organs after LPS injection in tolerant- and susceptible-to-hypoxia animals. After 3 hours of LPS administration, the tolerant-to-hypoxia rats showed no changes in the thymus, spleen, and subpopulation composition of lymphocytes in peripheral blood. After 6 hours there was only a decrease in B-lymphocytes and increase in cytotoxic T-lymphocytes and NK cells. After 1 day of LPS injection, the tolerant-to-hypoxia rats had devastation in PALS of the spleen. After 3 hours of LPS injection the susceptible-to-hypoxia animals had reactive changes in the lymphoid organs: decrease of the thymus cortex, narrowing of the marginal zones of spleen lymphoid follicles, widening of their germinal centers, and a decrease in the absolute number of cytotoxic T-lymphocytes, NK cells, and B-lymphocytes. After 24 hours of LPS injection the tolerant-to-hypoxia animals had a greater absolute number of T-lymphocytes and NK cells in comparison with the susceptible rats. Thus, in animals with different resistance to hypoxia the LPS-induced SIRS is characterized by different dynamics of morphological and functional changes of the thymus and spleen. The obtained data will serve as a basis for the development of new individual approaches to the prevention and treatment of infectious and inflammatory diseases.

Asthma is characterized by chronic inflammation in the airways. Several models have been proposed for the discovery of new therapies. Low-Level Laser Therapy (LLLT) is relatively new and effective, very low cost, with no side effects. However, there is still no consensus on the optimal dose to be used. In this sense, the objective of the present study was to evaluate the best dose in an experimental model of asthma induced by House Dust Mite (HDM). Balb/c mice received administration of 100 ug/animal HDM and LLLT applications (diode laser: 660 nm, 100 mW and four different energies 1J, 3J, 5J, and 7.5J) for 16 days. After 24 hours, we studied inflammatory, functional, and structural parameters. The results showed that LBI was able to modulate the pulmonary inflammation observed by reducing the number of cells in Bronchoalveolar Lavage Fluid (BALF) as well as reducing the percentage of neutrophils, eosinophils and T lymphocytes. On the other hand, LLLT increased the level of IL-10 and reduced levels of IL-4, IL-5 and IL-13 in BALF. LLLT was able to reduce the production of mucus, peribronchial eosinophils, collagen deposition, bronchoconstriction index, and bronchial and muscular thickening in the airways. We concluded that the use of LLLT in the treatment of chronic inflammation of the airways attenuated the inflammatory process and functional and structural parameters. We emphasize, in general, that the 1J and 3J laser presented better results. Thus, photobiomodulation may be considered a promising tool for the treatment of chronic pulmonary allergic inflammation observed in asthma.

Background: Familial Mediterranean Fever (FMF) is a hereditary autosomal recessive disease which is mainly seen in the Turks, Armenians, Arabs, and Jews. It is characterized by recurrent episodes of fever, polyserositis, and rash. MEFV gene, encoding pyrin protein, is located on the short arm of chromosome 16. FMF is associated with a broad mutational spectrum in this gene. Certain mutations are more common in particular ethnic groups. To date, different mutations of MEFV were observed in studies carried out in different regions worldwide. However, most of these studies did not extensively investigate the Egyptian population, in spite of the high prevalence of FMF in this geographical region.

Aim: To identify the frequency of MEFV gene mutations among the patients who presented with FMF like symptoms and, to characterize the different genetic mutations and their association with increased Amyloid A among Egyptian patients.

Methods: FMF Strip Assay (Vienna Lab Diagnostics, Vienna, Austria) was used. This test is based on reverse hybridization of biotinylated PCR products on immobilized oligonucleotides for mutations and controls in a parallel array of allele-specific oligonucleotides.

Results: Among the 1387 patients presenting with signs and symptoms suggestive of FMF, 793 (57.2%) were of undefined mutations, whereas 594 had MEFV gene mutations. 363 patients (26.2%) were heterozygous mutants, 175 patients (12.6%) were compound heterozygous mutants, and 56 patients (4%) were homozygous mutants. The most commonly encountered gene mutations in heterozygous and homozygous groups were E148Q (38.6%), M694I (18.1%), and V726A (15.8%). The most commonly encountered gene mutations in the compound heterozygous groups were E148Q+M694I observed in 20.6% of the patients, followed by M694I+V726A and M6801+V726A found in 18.9% and 11.4 %, respectively. The most commonly encountered gene mutation associated with abdominal pain, fever, and high serum Amyloid A was E148Q allele (37.5%).

Conclusions: Unlike all previous publications, E148Q allele was found to be the most frequent in the studied patients. Moreover, this allele was associated with increased Amyloid A. 793 patients were free of the 12 studied Mediterranean mutations, which implies the necessity to perform future sequencing studies to reveal other mutations.

Polycystic ovary syndrome is associated with dyslipidemia, dysglycemia, metabolic syndrome, and low-grade chronic inflammation, which increase the risks for cardiovascular disease. Combined oral contraceptives may affect the mediators of low-grade chronic inflammation with potential additive risk in PCOS patients. This meta-analysis investigates the impact of oral contraceptive on markers of chronic inflammation in PCOS patients. Pubmed, Scopus, and Cochrane database were used to search studies reporting on this matter in the target population. Twenty seven studies were selected, including a total of 838 women. The data were expressed as the standardized mean difference. The random-effects model was used to summarize effect sizes. Heterogeneity was examined using Cochran's test (Q) and I² statistics. Most of the preparations increased C-reactive protein (CRP) in PCOS patients (p >0.001). The increase in homocysteine levels was not significant (p >0.05). Follistatin significantly increased with pills containing cyproterone acetate (p= 0.008). Interleukin-6 changes were inconsistent and plasminogen activator inhibitor-1 decreased with pills containing desogestrel, norgestimate, and drospirenone. Collectively, the results of this review indicate that oral contraceptives modify most inflammatory markers of PCOS patients. However, the clinical implications are not clear yet and future studies must consider longer follow-up and the inclusion of objective clinical parameters.

Objectives: Familial Mediterranean Fever (FMF) is one of the most prevalent periodic fever syndromes; MEFV, the responsible gene for the disease, is in the short arm of chromosome16. In the considerable count of the FMF patients, only one mutation is found in the MEFV and parents, who were the obligatory carriers for that mutation, were asymptomatic. The aim of this study was to evaluate these asymptomatic parents in regard to mutation in MEFV gene and similarity between parents and offspring patients.

Methods: In this cross-sectional study, asymptomatic parents of FMF patients enrolled the study were referred to periodic fever clinic or pediatric rheumatology clinic of Tehran University of Medical Sciences. The patients should have at least one mutation in MEFV gene and none of them had any family history of autoinflammatory disease. Twelve mutations in MEFV gene were assessed in the parents by Vienna Lab FMF Strip Assay kit by MAS PCR/Reverse hybridization.

Results: Forty-three patients and their parents participated in the study. Sixty-three percent (27) of patients were male. Onset of disease symptoms in 31 patients (72%) was before 4 years of old. Nine (21%) of the patients had homozygote, 16 (37%) compound heterozygote, and 17(40%) heterozygote for MEFV mutation; there was a case of complex alleles mutations (2%). M694V/M694V in 4 patients (9%) was the most homozygote genotype, and M694V/R761H in 4 (9%) and E148Q in 7 (16%) were the most compound heterozygote and heterozygote genotype, respectively. M694V, M680I, and E148Q were the most mutation in the parents. Overall, 41 patients had mutations similar to their parents' mutation, except 2 whose parents had no mutation, but a patient did.

Conclusion: It seems that occurrence of new mutations in offspring is not prevalent among FMF patients and there are other reasons for different clinical presentation in similar mutation carriers. On the other hand, in ethnicities with high prevalence of FMF, new mutation in descendant may occur, infrequently.

Humanized mice are a state-of-the-art tool used to study several diseases, helping to close the gap between mice and human immunology. This review focuses on the potential obstacles in the analysis of immune system performance between humans and humanized mice in the context of severe acute inflammation as seen in sepsis or other critical care illnesses. The extent to which the reconstituted human immune system in mice adequately compares to the performance of the human immune system in human hosts is still an evolving question. Although certain viral and protozoan infections can be replicated in humanized mice, whether a highly complex and dynamic systemic inflammation like sepsis can be accurately represented by current humanized mouse models in a clinically translatable manner is unclear. Humanized mice are xenotransplant animals in the most general terms. Several organs (e.g., bone marrow mesenchymal cells, endothelium) cannot interact with the grafted human leukocytes effectively due to species specificity. Also the interaction between mice gut flora and the human immune system may be paradoxical. Often, grafting is performed utilizing an identical batch of stem cells in highly inbred animals which fails to account for human heterogeneity. Limiting factors include the substantial cost and restricting supply of animals. Finally, humanized mice offer an opportunity to gain knowledge of human-like conditions, requiring careful data interpretation just as in nonhumanized animals.

Background: Chronic obstructive pulmonary disease (COPD) is a devastating condition with limited pharmacotherapeutic options and exceptionally high public-health burden globally as well as in India. Tobacco smoking is the primary cause for COPD among men in India. Systemic inflammation involving altered regulation of cytokines controlling the host defense mechanism is a hallmark of COPD pathogenesis. However, biomarker discovery studies are limited among Indian COPD patients.

Methods: We assessed the serum concentrations [median (25th-75th percentile) pg/ml] of interleukin (IL)-2,4,6,8,10, granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) using a multiplexed immunoassay. Our study cohort consisted of 30 tobacco smokers with COPD (TS COPD) and 20 tobacco smokers without COPD (TS CONTROL) from South India. The study population was matched for age, sex (male), and tobacco consumption (pack-years). COPD was diagnosed according to the global initiative for chronic obstructive lung disease (GOLD) criteria of persistent airflow obstruction determined by the ratio of postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV₁/FVC) of <0.7. A validated structured questionnaire-based survey [Burden of Obstructive Lung Disease (BOLD) study] and spirometry were performed during house to house visit of the field study. Statistical analysis included nonparametric (two-tailed) Mann-Whitney U and Spearman rank test, as appropriate (significance: p<0.05).

Results: Serum GM-CSF [69.64 (46.67, 97.48); 36.78 (30.07, 53.88), p=0.014], IFN-γ [51.06 (17.00, 84.86); 11.70 (3.18, 32.81), p=0.017], IL-4 [9.09 (1.8, 19.9); 1.8 (1.8, 4.46); p=0.024], and TNF-α [20.68 (5.5, 29.26); 3.5 (3.5, 4.5); p<0.001] concentrations (pg/ml) were increased in TS COPD subjects compared to TS CONTROL. A weak correlation between lung function parameters and cytokine concentrations was detected.

Conclusion: Our pilot study reveals GM-CSF, IFN-γ, IL-4, and TNF-α as plausible COPD susceptibility biomarkers within the investigated South Indian population that needs to be validated in a larger cohort.

Maerua angolensis has been used traditionally in the management of pain, arthritis, and rheumatism in Ghana and Nigeria but no scientific evidence is currently available to give credence to its folkloric use. The aim of this study was therefore to evaluate the anti-inflammatory effects of a stem bark extract of Maerua angolensis DC (MAE) in acute inflammatory models. The effects of MAE (30-300 mg kg^-1) on neutrophil infiltration, exudate volume, and endogenous antioxidant enzymes in lung tissues and lung morphology were evaluated with the carrageenan induced pleurisy model in Sprague Dawley rats. The effects of MAE (30-300 mg kg^-1) on vascular permeability were also evaluated in the acetic acid induced vascular permeability in ICR mice. MAE significantly reduced neutrophil infiltration, exudate volume, and lung tissue damage in carrageenan induced pleurisy. MAE increased the activities of antioxidant enzymes glutathione, superoxide dismutase, and catalase in lung tissues. The extract was also able to reduce myeloperoxidase activity and lipid peroxidation in lung tissues in carrageenan induced rat pleurisy. Vascular permeability was also attenuated by the extract with marked reduction of Evans blue dye leakage in acetic acid induced permeability assay. The results indicated that Maerua angolensis is effective in ameliorating inflammation induced by carrageenan and acetic acid. It also has the potential of increasing the activity of endogenous antioxidant enzymes.