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Increased interleukin-6 levels in cerebrospinal fluid following subarachnoid hemorrhage.

Serum and cerebrospinal fluid (CSF) samples from 12 patients were analyzed for interleukin (IL)-6, soluble IL-2 receptor (IL-2R), and soluble CD8 levels in order to determine the immune activation profile following subarachnoid hemorrhage (SAH). Dramatically increased levels of IL-6 and moderate increases of soluble IL-2R were detected in the CSF in 11 of the 12 patients; slightly elevated levels of soluble CD8 were observed in six patients. The IL-6 levels were higher on Day 6 than on Days 3 and 9. The increases in IL-6, soluble IL-2R, and soluble CD8 levels in the CSF samples were not paralleled by increased values in the serum samples, and thus probably reflected an intrathecal synthesis of the cytokine. Passive transfer of IL-6 across the blood-brain barrier seemed not to occur since the serum and CSF levels of IL-6 showed a negative correlation. The findings suggest a severe inflammatory affection of the central nervous system that could be of importance in understanding the clinical course in patients following SAH.

Adult↗

Cutting edge: altered pulmonary eosinophilic inflammation in mice deficient for Clara cell secretory 10-kDa protein.

Clara cell secretory protein (CC10) is a steroid-inducible protein, and its in vivo function is currently unclear. The role of CC10 in modulation of pulmonary allergic inflammation was examined in mice deficient for the CC10 gene. Wild-type and homozygous CC10-deficient mice were sensitized with an Ag, OVA, and challenged with either OVA or saline. When compared with that seen in wild-type mice, a significantly higher level of pulmonary eosinophilia was found in Ag-sensitized and challenged CC10-deficient mice. Significantly increased levels of Th2 cytokines IL-4, IL-5, IL-9, and IL-13 were also found in CC10-deficient mice. In addition, an increased level of eotaxin, but not RANTES, was also seen in CC10-deficient mice. No significant difference was observed in the level of a Th1 cytokine, IFN-gamma, between different groups of mice. These results provided the first in vivo evidence that CC10 plays a role in the modulation of pulmonary allergic inflammation.

Animals↗

Myeloid differentiation factor 88 is required for cross-priming in vivo.

We describe a role for myeloid differentiation factor 88 (MyD88) in the induction of functional CTLs in vivo, in response to exogenously administered Ag, using a heat shock fusion protein, hsp65-P1, as a model Ag. CD8 T cells transferred into MyD88-deficient animals produce normal numbers of CD8 effector cells that have normal activation marker profiles after immunization with hsp65-P1. However, these CD8 T cells produced significantly less IFN-gamma and showed reduced killing activity. This reduction in activation of functional CTLs appears to be unrelated to Toll-like receptor 4 function, because in vitro hsp65-P1-experienced Toll-like receptor 4-deficient dendritic cells (DCs), but not MyD88-deficient DCs, activated CD8 T cells to a similar extent to wild-type DCs. We identify a cross-presentation defect in MyD88-deficient DCs that, when treated with hsp65-P1 fusion protein, results in surface display of fewer SIYRYYGL/class I MHC complexes. Thus, MyD88 plays a role in the developmental maturation of DCs that allows them to prime CD8 T cells through cross-presentation.

Adaptor Proteins, Signal Transducing↗

Assessment of physiological stress in periparturient cows and neonatal calves.

Pregnancy is considered to be one of the physiological stressors. The stress hormone, cortisol is significantly involved in various events during periparturient period including initiation of parturition. The study was conducted to estimate the serum cortisol concentration in cows and the neonatal calves in order to correlate the effect of cortisol on certain haematological and biochemical parameters such as blood glucose level (BGL), total plasma protein (TPP), lymphocyte:neutrophil ratio and mitogen induced lymphocyte proliferative response. Blood samples were collected from six cows in four periods, namely., 3 days prior to parturition, on the day of parturition, and 7 days after parturition. Blood samples were also collected from neonatal calves in the period 0, 7 and 14 days of age. Calves above two months of age and non-pregnant dry cows were considered as the controls. The serum cortisol concentration in cows on the day of parturition was significantly higher (P < 0.01) than controls and the value in calves was also significantly higher (P < 0.01) at 0 day than their controls. On the day of parturition BGL level of the dam and calves were significantly higher (P < 0.01), whereas the proliferative response of lymphocytes to mitogen was significantly lower (P < 0.01) than controls. However TPP levels did not differ significantly. This confirmed that the dam at the time of parturition and neonatal calf before taking colostrum are under a high risk of infection because of the low profile of immune status. The lymphocyte:neutrophil ratio also justified the above suggestion.

Animals↗

[A comparative analysis of changes in immune homeostasis in laparoscopic and conventional surgical interventions on the large intestine].

A comprehensive evaluation has been done of parameters characterizing cell-bound immunity, cytokinic profile, stress hormones (hydrocortisone), and C-reactive protein in a comparative aspect in those patients having undergone laparoscopic or conventional colectomy. The above indices were determined before surgery, in the early postoperative period, 24 h and 7 days subsequent to surgery. Laparoscopic surgical intervention was found out to lower somewhat the level of immunosuppression early in the postoperative course, which fact is manifested by retaining of expression HLA-DR on monocytes of the peripheral blood. Further randomized investigations should allow the final judgement about the degree of surgical stress.

Adult↗

[Non alcoholic steatohepatitis: a multifactorial, frequent, paucysymptomatic liver disease with a fibrotic outcome].

BACKGROUND: The aim of this study was to evaluate the morphological, clinical and biochemical characteristics of non alcoholic steatohepatitis to understand its pathogenesis. PATIENTS AND METHODS: From January 1993 to June 2000, 44 patients were selected on histological criteria. Alcohol intake, blood pressure, weight, glycaemia, lipid, immune, iron profiles hemochromatosis (HFE) gene mutations were analyzed. Patients were re-examined thereafter or in June 2000. RESULTS: Twenty one women and 10 men were included (mean age=54). Nineteen patients were asymptomatic (61.3%). Patients often presented with an increase in alanine aminotransferase. This was correlated with steatosis (P=0.008). Hypertension, excess weight, abnormal serum glucose levels and dyslipidaemia were respectively observed in 10 (32.2%), 24 (77.4%), 16 (51.6%) and 18 (58.1%) patients. Thirteen of these patients (41.9%) presented abnormal autoantibodies titers without autoimmune hepatitis; 18 (58.1%) presented an iron overload. A mutation of the HFE gene was detected in 14 of 25 patients (51.6%). Liver iron concentrations were not correlated to the extent of fibrosis extension or with mutations. CONCLUSION: Increased alanine aminotransferase levels usually revealed non alcoholic steatohepatitis. A high prevalence of autoantibodies, iron overload and mutation of the HFE gene were detected. Non alcoholic steatohepatitis should be diagnosed because it can be associated with cirrhosis.

Alanine Transaminase↗

Study of HLA-DR expression on skin lesions of leprosy before and during multiple drug therapy.

Leprosy is a dynamic disease in which cell mediated immunity (CMI) plays an important role in host defense and control of the clinical spectrum. This study was carried out to detect immune activation in the granuloma of leprosy during multiple drug therapy (MDT) by studying the expression of human leukocytic antigen-DR (HLA-DR) in the granuloma before and during therapy. Skin punch biopsies were taken before and at least once 2-4 weeks after starting MDT in 20 newly diagnosed patients. Two biopsies, 2-4 weeks apart, were also taken from 10 new patients who did not yet receive any treatment, for comparison. Furthermore, biopsies were taken before and during corticosteroid therapy in five patients who developed reversal reaction during MDT. The biopsy specimens were studied for the expression of HLA-DR using the immunofluorescent staining which was found to be visibly increased in 17 out of 20 new cases (85%) within 2-4 weeks after starting MDT, while no change in the expression was noticed in those who did not receive any treatment (p < 0.001). This might reflect the increased production of interferon gamma (IFN gamma) specially from granuloma lymphocytes after being stimulated with the excessive release of mycobacterial antigen from killed bacilli during therapy. The five patients who developed reversal reaction during MDT had strong HLA-DR expression in the first biopsies which declined subsequently 2-6 weeks after starting prednisolone therapy. Our results suggest that CMI was activated in skin lesions of leprosy during MDT. Such activation was not only restricted to those who developed reversal reaction across the therapeutic course, which indicates that the difference between patients who developed such reaction and those who did not, was likely to be quantitative rather than qualitative, with a more exaggerated CMI response in the former. Furthermore, it seems that the beneficial effect of MDT is accompanied by important changes in the immune cell profile which have a great role in overcoming such infection.

Adolescent↗

The mouse as a model for investigation of human granulocytic ehrlichiosis: current knowledge and future directions.

The use of laboratory mice to investigate correlates of infectious disease, including infection kinetics, cellular alterations, cytokine profiles, and immune response in the context of an intact host has expanded exponentially in the last decade. A marked increase in the availability of transgenic mice and research tools developed specifically for the mouse parallels and enhances this research. Human granulocytic ehrlichiosis (HGE) is an emerging, zoonotic disease caused by tick-borne bacteria. The HGE agent (Anaplasma phagocytophila) is one of two recognized pathogens to cause human granulocytic ehrlichiosis (HGE). The mouse model of HGE complements in vitro tissue culture studies, limited in vivo large animal studies, and ex vivo studies of human and ruminant neutrophils, and promises new avenues to approach mechanisms of disease. In the overview reported here, we focus principally on current research into HGE pathogenesis using the mouse model. Included is a discussion of current changes in ehrlichial classification and nomenclature, a review of ehrlichial biology and ecology, and highlights of clinical disease in animals and people.

Anaplasma phagocytophilum↗

Antitumor effects produced by transduction of dendritic cells-derived heterodimeric cytokine genes in murine colon carcinoma cells.

Interleukin (IL)-23 and IL-27 have been recently identified as members of the IL-12 heterodimeric cytokine family. The cytokines are released from activated dentritic cells and play a crucial role in cell-mediated immunity. Expression profiles of the cytokines' receptors suggest that target cells of the cytokines are distinct depending on T cell maturation and differentiation. We first examined whether murine colon carcinoma cells (Colon 26) expressing IL-27 (Colon 26/IL-27) could produce antitumor effects in syngeneic mice. The mice developed small Colon 26/IL-27 tumors and subsequently rejected them, whereas parent tumors continued to grow. Since Colon 26/IL-12 and Colon 26/IL-23 cells were also rejected in syngeneic mice, we then investigated the combinatory antitumor effects of the cytokines. We inoculated Colon 26/IL-12, Colon 26/IL-23, Colon 26/IL-27 cells or mixed populations of the cytokine producers into one flank of the mice that simultaneously received parent tumors in the other flank. The parent tumor growth influenced by the cytokine producers was similar to each other. Combinatory antitumor effects were not produced by the cytokine producers and application of the cytokines did not show any synergistic effects.

Animals↗

[Use of correlation analysis of clinical and laboratory data in the treatment of patients with chronic suppurative maxillary sinusitis].

In order to objectivize clinical and laboratory data, we applied P. V. Terentyev's method of correlation analysis as modified by A. N. Zosimov when examining 60 adolescents with chronic purulent maxillary sinusitis. This approach was necessary to choose an adequate method for evaluating the therapeutic efficacy. Analysis of correlations between clinical parameters, blood profile and immune data demonstrated different relationships before and after therapy. The mathematical and graphical models proposed make it possible to evaluate objectively each type of treatment, the results being in agreement with clinical observations. These models can help predict the course of disease.

Adolescent↗

Two divergent routes of evolution gave rise to the DRw13 haplotypes.

The HLA class II genes and haplotypes have evolved over a long period of evolutionary time by mechanisms such as gene conversion, reciprocal recombination and point mutation. The extent of the diversity generated is most clearly evident in an analysis of the HLA class II alleles present within DRw13 haplotypes. This study uses cDNA sequencing to examine the first domains of DRB1, DRB3, DQA1, and DQB1 alleles from several American black individuals expressing seven different DRw13 haplotypes, five with undefined HLA-D specificities (i.e., not Dw18 or Dw19). Two new DRw13 alleles described in this study are the first examples of convergent evolution of DR alleles in which gene conversion has apparently combined segments of DRB1 alleles encoding DRw11 and DRw8 to generate two new DRB1 alleles, DRB1*1303 and DRB1*1304, that encode molecules bearing serologic determinants of a third allele, DRw13. These new DRw13 alleles are found embedded in haplotypes of DRw11 origin distinct from haplotypes encoding previously identified DRw13 alleles, DRB1*1301 and DRB1*1302. These data suggest that two evolutionary pathways may have given rise to two subgroups of alleles encoding molecules that share DRw13 serologic determinants yet which possess different structural and, likely, functional motifs. Reciprocal gene recombination events resulting in different DR, DRw52 and DQ allele combinations also appear to have played a crucial role in augmenting the level of diversity found in DRw13 haplotypes. Recombination has resulted in the association of one of the new DRw13 alleles with a DQw2 allele normally found associated with DR7 and the association of the DRw52c-associated DRw13 allele (DRB1*1302) with three different DQw1 alleles. The seven DRw13 haplotypes that have resulted from the effect of recombination on haplotypes formed by the two pathways of DRw13 allelic diversification have resulted in different repertoires of class II molecules and, most likely, different immune response profiles in individuals with these haplotypes.

Alleles↗

[Pleuropulmonary tumors. Presentation of 2 cases with peculiar clinicopathologic traits].

A pseudomesotheliomatous adenocarcinoma, which is a rare form of peripheral pulmonary tumor with diffuse thickening of the pleural cavity mimicking a mesothelioma, and a malignant mesothelioma with a carcinoma like disseminating pattern are presented. The biopsy obtained by thoracotomy in one case, and the necropsy studies enabled the diagnosis by the microscopic pattern, the presence of mucosubstances (PAS diastase) and the immune histochemical profiles with antibodies against several antigenic groups (CEA, EMA, CAM 5.2, and Vimentin. The value of these techniques to differentiate adenocarcinomas and mesotheliomas is discussed. The presence of CEA orients to an epithelial origin of a neoplasia.

Adenocarcinoma↗

Immune monitoring of blood in heart transplant recipients: application of flow cytometry.

In this study, we review the utility of peripheral blood lymphocyte evaluation using commercially available monoclonal antibodies in the diagnosis of rejection or infection in 27 patients undergoing allograft heart transplantation. Double-color staining methods employing fluorescein isothiocyanate (FITC) and phycoerythrin (PE) allowed identification of a variety of lymphocyte subsets and determination of activation or proliferation of lymphocytes. All patients also underwent regular endomyocardial biopsy procedures. A total of 30 rejection episodes were diagnosed by endomyocardial biopsy. The results of immune monitoring profile (IMP) of lymphocytes and endomyocardial biopsies were concordant 76% of the time. Discrepancies were most common when the biopsy showed only mild rejection. The false-positive rate with serial IMP was less than 1%. The IMP was also useful in distinguishing between infection, especially cytomegalovirus infection, and rejection. General guidelines for utilizing IMP in transplant recipients are presented.

Antibodies, Monoclonal↗

Cell-mediated immunity in the acquired immunodeficiency syndrome.

The present study evaluates the in vitro cellular immunity response in cases of suspected Acquired Immunodeficiency Syndrome (AIDS). The immunological features of 111 patients were correlated with those from eleven healthy controls. Patients were divided into three groups: RISK, LAS/ARC and AIDS, using CDC criteria. The AIDS showed leucopenia, lymphopenia, diminished number of T and B lymphocytes, normal number of thermostable E-rosette forming cells (TE), decreased helper-inducer T cell, elevated suppressor-cytotoxic T cell, reversed helper T cell/suppressor T cell ratio and depressed proliferative response using mitogens like phytohemagglutinin (PHA), concanavalin-A (Con-A), pokeweed mitogen (PWM) and purified protein derivative antigen (PPD). These findings confirm a severe deficiency in cellular immunity and permit to establish an immune cellular profile, characteristic of the AIDS patients.

AIDS-Related Complex↗

[Local and systemic antibody response after vaccination with 3 different types of vaccines against influenza I. Hemagglutinationinhibiting antibodies (author's transl)].

A comparative study on the formation of hemagglutination inhibiting antibodies after vaccination with 3 different types of Influenza Vaccines (Whole virion, Splitvirion, and Subunit type) was performed in adults and children. The study populations were homogeneous as regards age and pre-immunization antibody profile. The following results were obtained: 1) Strain specific conversion rates for the A component (A/Victoria/3/75 H3N2) were 77% with the whole virion vaccine, 79% with the Splitvirion vaccine and 91% with the Subunit vaccine. The antibody conversion factors calculated on the basis of the geometric mean titers (GMT) were 5.0, 6,7 and 9.0 respectively. A fourfold increase in titers was observed in 68% of vaccinees with the whole virion vaccine, in 55% of vaccinees with the Splitvirion vaccine, and in 70% of vaccinees with the Subunit vaccine. 2) Local antibody formation on the basis of conversion rates yielded values of 18% (whole virion), 22% (Splitvirion), and 28% (Subunit vaccine). 3) Systemic antibody responses revealed predominantly strain and subtype specificity as opposed to local antibody formation which was also directed towards older sybtypes. This phenomenon was more pronounced in adults than in children. 4) A significant correlation was found between the local antibody production and the concentration of hemagglutination inhibiting serum antibodies as well as between the IgA concentration in nasal wash fluid and the percentage of individuals exhibiting local antibody formation in the upper respiratory tract system. 5) In children 6-14 years of age the antibody conversion rates were found to be 91-100% for the A component with the 3 vaccines under study. The GMT for the respective vaccines A, B and S ranged from 1:170 over 1:139 to 1:211. 6) With regard to the induction of hemagglutination inhibiting antibodies to the B component of the vaccine (B/Hongkong/8/73) either vaccine proved to be of insufficinet potency. Though conversion rates of 6/ to 77% (60-90% in children) were observed the GMT range was only 1:17 to 1:21 (1:21 to 1:35 in children). Only 29 to 35% of the adults and about one half of the children developed antibodies of greater than or equal to 1:40 after vaccination. With regard to this observation it has to be discussed whether one shouldn't consider monovalent A vaccines for future use in influenza vaccination campaigns.

Adolescent↗

[Immunological reactivity to the products of normal microflora. III. Characteristics of antibodies to the common antigens of enterobacteria, enterococci and bifidobacteria].

The content and type of antibodies to the common antigens of enterobacteria, enterococci and bifidobacteria were studied in serum specimens obtained from 220 donors. Antibody titers to enterobacteria were almost twice as high as those to enterococci and 8 times higher than those in bifidobacteria. The final titer of the reaction with enterobacterial antigens in 90% of the donors was determined by IgG (7S); in respect of enterococci and bifidobacteria IgM played the leading role in 56% and 74% of the cases, respectively. In most cases the profile of immune responsiveness was characterized by marked individuality and comprised various titers and types of antibodies to the antigens of all three groups of bacteria. The results thus obtained are analyzed from the viewpoint of normal responsiveness to standard immunological stimuli; all individuals come in contact with such stimuli with an equal degree of probability.

Antibodies, Bacterial↗

The immunomodulatory effect of topical cyclosporin A in atopic keratoconjunctivitis.

PURPOSE: To perform a detailed examination of the immunomodulatory effects of topical cyclosporin A (CsA) in conjunctival tissue from patients with atopic keratoconjunctivitis (AKC). METHODS: Patients with active AKC were randomly allocated into two groups of four patients. For 3 months one group received 2% CsA drops, and the other group received placebo drops. Superior tarsal conjunctival biopsy specimens were harvested before and after treatment and examined by one- and two-color immunohistochemistry to compare leukocyte counts, HLA-DR+ and IL-2R+ cell counts, HLA-DR positivity of conjunctival epithelial cells, and counts of T cells expressing the cytokines interleukin (IL)-2, IL-3, IL-4, IL-5, and interferon (IFN)-gamma. RESULTS: Posttreatment values were significantly less than pretreatment values for the total number of leukocytes and in the numbers of CD3+ T cells, CD4+ cells, CD8+ cells, CD20+ B cells, neutrophils, and macrophages, and there was a decrease in the CD4-CD8 ratio (P = 0.03) in the CsA group. There was a reduction from before CsA treatment to after CsA-treatment in the numbers of HLA-DR+ and IL-2R+ cells (P = 0.03), but the reduction in the epithelial cell HLA-DR expression did not reach significance. The number of T cells staining for IL-3 and IL-5 was reduced, although not to statistical significance, but there was a significant reduction in the number of T cells expressing IL-2 and IFN-gamma (P = 0.03) after CsA treatment compared with initial values. There were no statistically significant differences between pretreatment and posttreatment values in the placebo group. There was a clinical improvement in the CsA group and a clinical worsening in the placebo group. CONCLUSIONS: The in vitro effects of CsA translate into a reduction in T cells, a normalization of the CD4-CD8 ratio, a decrease in T-cell activation, and a reduction in T-cell cytokine expression, especially IL-2 and IFN-gamma. The decrease in HLA-DR expression may be mediated by the change in IFN-gamma. There were fewer B cells but not fewer plasma cells after CsA and no change in IL-4 expression, suggesting minimal effects on type I hypersensitivity responses. There was no significant reduction in mast cell or eosinophil numbers, but direct effects of topical CsA on their function may play a role in the therapy of ocular allergic disease. These results show that the beneficial effects of topical CsA in AKC are accompanied by important changes in conjunctival immune cell profiles.

Administration, Topical↗