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Biomedical subjects

O Strannegård

Publications and source records attributed to O Strannegård.

At least 19 recordsLinked to original sources
PubMed2005

Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.

OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.

Adolescent↗
PubMed2000

Low levels of interferon-gamma in nasal fluid accompany raised levels of T-helper 2 cytokines in children with ongoing allergic rhinitis.

The T-helper 2 (Th2) cytokines interleukin-(IL-) 4, IL-5, IL-6, IL-10 and the Th1 cytokine IFN-gamma and their associations with eosinophil, eosinophil cationic protein (ECP) and immunoglobulin (Ig) E were studied in nasal lavage fluid from 60 school children with allergic seasonal rhinitis and 36 nonatopic healthy controls, before and during the pollen season. Eosinophil differential counts and IgE increased significantly in the patients during the pollen season. The eosinophil differential counts, ECP and IgE were all significantly higher during the season than in specimens simultaneously obtained from the nonatopic controls. Before season, the levels of ECP and IgE, but not eosinophils, were significantly higher in the patients than in the controls. During the season the nasal lavage fluid levels of IFN-gamma were significantly lower and the IL-4/IFN-gamma quotients significantly higher in the allergic than in the control children. In the allergic children, but not in the controls, the nasal fluid levels of the Th2 cytokines IL-4, IL-5 and IL-10 increased during the season, and together with IL-6, were correlated with the differential counts of eosinophils, and with the levels of ECP and IgE. These findings are compatible with the hypothesis that a deficient release of the Th1 cytokine IFN-gamma plays an important role in the pathogenesis of allergic inflammation. Regardless of whether the defective IFN-gamma secretion is primary or a consequence of suppression by other cytokines, it will in the atopic subjects enhance the release of Th2 cytokines, which in turn will facilitate the development of allergic inflammation.

Adolescent↗
PubMed2000

Topical steroid treatment of allergic rhinitis decreases nasal fluid TH2 cytokines, eosinophils, eosinophil cationic protein, and IgE but has no significant effect on IFN-gamma, IL-1beta, TNF-alpha, or neutrophils.

BACKGROUND: Topical treatment with glucocorticoids (GCs) is known to decrease eosinophils but not neutrophils in patients with allergic rhinitis. OBJECTIVE: We sought to examine whether the differential effects of GC treatment on eosinophils and neutrophils are mirrored by differential effects on T(H)1/T(H)2 cytokines and the neutrophil-associated cytokines IL-1beta and TNF-alpha. METHODS: Differential counts of eosinophils and neutrophils in nasal fluids from 60 children with seasonal allergic rhinitis treated with a topical GC were examined after staining with May-Grünwald-Giemsa stain. Nasal fluid levels of IFN-gamma, IL-4, IL-6, IL-10, IL-1beta, and TNF-alpha were examined with ELISA, and IgE and eosinophil cationic protein (ECP) levels were examined with RIA. RESULTS: After GC treatment, there was a statistically significant decrease of the T(H)2 cytokines IL-4, IL-6, and IL-10, as well as ECP and IgE. By contrast, there were no significant changes of the levels of IFN-gamma, IL-1beta, TNF-alpha, or neutrophils. In the GC-treated patients IL-1beta and TNF-alpha levels correlated with neutrophils and ECP, and IL-1beta correlated with eosinophils. Furthermore, ECP correlated with both eosinophils and neutrophils. Neither IL-1beta nor TNF-alpha correlated with IgE. Patients with high neutrophil counts after GC treatment were found to have significantly higher eosinophil counts and ECP than patients with low counts. CONCLUSIONS: The beneficial effects of topical treatment with GC in patients with allergic rhinitis could be attributed to downregulation of T(H)2 cytokines, with an ensuing decrease of eosinophils, ECP, and IgE. It is possible that neutrophils could counteract the beneficial effects of GCs by releasing the proinflammatory cytokines IL-1beta and TNF-alpha.

Administration, Topical↗
PubMed1999

[Why is the prevalence of allergy increasing? Changed microbial load is probably the cause].

The prevalence of allergic disease is increasing dramatically in industrialised countries. Environmental factors that are putative causes of this increase are to be sought among those that induce a shift in T-helper cell (Th1/Th2) balance toward Th2 immunity dominance, and whose natural occurrence is consistent with epidemiological evidence of regional differences in allergy prevalence. Of such factors, changes in the panorama of bacterial and viral infections, altered intestinal microflora, and changes in dietary habits (particularly increased consumption of omega-6 fatty acids) seem to be the most likely causes of the increased prevalence of allergic diseases. There are also other factors, however, such as diesel exhaust particles, tobacco smoke and environmental toxins, which may partly fulfil the immunological and epidemiological criteria. As several of these putative environmental factors exert powerful effects in vitro, the increase in allergy prevalence is hardly surprising.

Air Pollutants↗
PubMed1999

Interleukin-5 and interleukin-8 in relation to eosinophils and neutrophils in nasal fluids from school children with seasonal allergic rhinitis.

The objectives of this study were to measure interleukins 5 and 8 (IL-5 and IL-8) in relation to eosinophils and neutrophils, in nasal lavage fluids from 60 school children with allergic rhinitis, and to determine the influence of treatment with a topical steroid (budesonide) on the levels of the two cytokines. Highly sensitive enzyme immunoassays were used to analyze IL-5 and IL-8. IL-5 levels and relative eosinophil counts in nasal lavage fluid increased significantly in patients with allergic rhinitis during the pollen season, compared with values obtained before the start of the season, and decreased significantly after treatment with budesonide. By contrast, no significant changes in IL-8 or neutrophils were found during the pollen season, nor did they decrease following treatment. In the untreated patients, IL-5 levels correlated significantly with eosinophil counts but not with neutrophil counts, whereas IL-8 levels correlated with neutrophil counts but not with eosinophil counts. After budesonide treatment, the correlation between IL-8 and neutrophils remained, and a correlation between IL-8 and eosinophils emerged. These findings support the concepts that IL-5 has a key role in regulating eosinophils and that IL-8 is important for the regulation of neutrophils. Whereas IL-5 and relative eosinophil counts are profoundly affected by topical steroid treatment, IL-8 and neutrophils are not demonstrably affected by such treatment. It is possible that neutrophils, through the release of IL-8, could be chemotactic for eosinophils in steroid-treated patients.

Adolescent↗
PubMed1998

Prevalence of allergy in children in relation to prior BCG vaccination and infection with atypical mycobacteria.

By influence on the Th1/Th2 cell balance, infectious agents may affect the development of atopic allergy. In this study, we investigated whether previous BCG vaccination or infection with atypical mycobacteria might be related to the development of atopic disease. The study, which involved skin testing with mycobacteria and answers to a questionnaire for more than 6000 children in Sweden, revealed a low prevalence of allergy among BCG-vaccinated children who were immigrants or adopted from other countries. Vaccinated children born in Sweden, however, did not have significantly lower allergy prevalence than age-matched, unvaccinated children. Furthermore, the overall frequencies of skin-test reactivity to the atypical mycobacteria M. avium and M. scrofulaceum were higher rather than lower in allergic than in nonallergic children. By contrast, there was a tendency toward a lower frequency of more strongly positive skin reactions (> or = 10 mm) to mycobacteria in allergic than in nonallergic children. These findings do not support the hypothesis that early mycobacterial infections have a suppressive effect on the development of atopic disease. Earlier findings of an apparent association between atopy and lack of previous mycobacterial infection may possibly be explained by a relatively decreased ability of atopic patients to mount strong Th1 cell-mediated immune responses.

BCG Vaccine↗
PubMed1997

Rotavirus infections in young Nicaraguan children.

BACKGROUND: Rotavirus is an important cause of dehydrating diarrhea in young children throughout the world. Knowledge about frequency of reinfections, development of immunity to the virus and the possible protective effect of breast milk is important, in particular in relation to possible strategies for immunization. METHODS: A prospective study of rotavirus infections in a cohort of 235 infants followed from birth until 2 years of age was performed in León, Nicaragua. Fecal and serum specimens were collected at specified times, and stools were also obtained during episodes of diarrhea. Fecal specimens were screened by rotavirus antigen detection and serum and colostral specimens were analyzed by isotype-specific rotavirus antibody enzyme-linked immunosorbent assay. RESULTS: As judged by anti-rotavirus IgA antibody seroconversion and/or demonstration of rotavirus antigen in fecal specimens, > 50% of the babies had evidence of past rotavirus infection by the age of 2 months. The total incidence of rotavirus infections, including many reinfections, was 0.7 infection/child-year, of which only 17% were associated with diarrhea. The time from birth to the first demonstration of rotavirus in stool samples correlated significantly with the concentration of anti-rotavirus IgA antibodies in colostrum. There was also a tendency toward a relationship between long duration of breast-feeding and asymptomatic infection. CONCLUSIONS: Rotavirus infections are acquired very early in infants in León, Nicaragua, and reinfections are common. Most infections are asymptomatic. Breast milk appears to confer partial protection against rotavirus infection, probably mediated by specific IgA antibodies. To be effective rotavirus vaccination would probably have to be given at a very early age to infants in developing countries.

Antibodies, Viral↗
PubMed1997

Association between pronounced IgA response in RSV bronchiolitis and development of allergic sensitization.

Forty-five children who had been hospitalized with bronchiolitis caused by respiratory syncytial virus (RSV) at a mean age of 4 months, and 90 matched control children, were tested for occurrence of RSV antibodies at one year of age. Of the children who had suffered from bronchiolitis, forty had demonstrable IgG antibodies, whereas the remaining five only had IgA antibodies against RSV. In the control group, 42% were RSV seropositive. The anti-RSV IgA antibody titres tended to be higher in patients with bronchiolitis than in controls and a larger proportion of the seropositive children in the former than in the latter group had demonstrable IgG antibodies. These findings suggest that RSV infections causing bronchiolitis are more often associated with a strong antibody response than are mild cases of the infection. Follow-up of the children at 3 years of age showed that allergic sensitization and development of asthma had occurred much more frequently in children with past RSV bronchiolitis than in controls. Children with past RSV bronchiolitis who later developed allergic sensitization had elevated RSV IgA antibody titres at one year of age more frequently than children with past RSV-bronchiolitis, who were not sensitized (p = 0.015). No significant differences regarding IgG antibody titres were observed. Since IgA, similarly as IgE, antibody formation is strongly Th2 cell dependent, the results are compatible with other findings suggesting that RSV has an unusual propensity to activate the Th2 cell system. This may contribute to the pathological picture of bronchiolitis in small children and at the same time render the infected child predisposed for later development of allergic sensitization. RSV bronchiolitis may thus be an important risk factor for later development of atopic disease although it cannot be excluded that the bronchiolitis simply serves as a marker that predict later development of atopy.

Antibodies, Viral↗
PubMed1997

Cytokines in nasal fluids from school children with seasonal allergic rhinitis.

Allergic rhinitis is a particularly good model for studies of cytokine production in vivo. In this study the occurrence of the cytokines IL-4, IL-5, IL-10 and IFN-gamma as well as the soluble receptor for IL-4 in nasal lavage fluids were assayed in 38 school children, with seasonal allergic rhinitis, and 19 healthy age-matched, non-atopic controls, using highly sensitive enzyme immunoassays. IL-4 levels in patients with seasonal allergic rhinitis were markedly increased in comparison with those in non-atopic controls or in atopic patients before the start of the pollen season. In controls, but not in the atopic patients, levels of IFN-gamma and IL-5 were significantly higher in specimens obtained during the pollen season than in those obtained outside the season. The IL-4/IFN-gamma ratios were significantly higher in atopic than in non-atopic subjects and further increased in atopic patients during the season. In addition to IL-4, elevated levels of IL-10 were observed in association with seasonal rhinitis. Following treatment with a topical steroid (budesonide) there was a statistically significant increase of the levels of soluble IL-4 receptor. These findings indicate that nonatopic and atopic individuals react to pollen exposure with distinct cytokine patterns in agreement with the Th1/Th2 concept. Topical steroids may possibly decrease inflammation by increasing the formation of soluble IL-4 receptor.

Adolescent↗
PubMed1996

Urinary eosinophil protein X in children with atopic asthma: a useful marker of antiinflammatory treatment.

BACKGROUND: Bronchial asthma is associated with elevated serum levels of eosinophil products, such as eosinophil protein X (EPX), but the occurrence in urine of this substance in patients with asthma has not previously been studied. OBJECTIVE: This study was performed to clarify whether increased amounts of eosinophil granulocyte proteins in urine and serum reflect ongoing asthmatic inflammation and whether decreasing values reflect successful treatment. METHODS: Twelve children with a median age of 12.5 years who had mild or moderate atopic asthma were studied for 3 months. At the time of inclusion in the study, treatment with inhaled budesonide was initiated. Nine children of the same age without atopic disease served as control subjects. Levels of EPX, eosinophil cationic protein (ECP), and myeloperoxidase in serum and in urine (urinary EPX) were determined at inclusion and then after 3 months of treatment. Spirometry was performed on the same occasions. RESULTS: At the time of inclusion, urinary EPX and serum ECP were significantly higher in children with atopic asthma than in the control subjects (mean, 116.4 vs 43.0 micrograms/mmol creatinine [p = 0.004] and 37.0 vs 14.8 micrograms/L [p = 0.004]). In the asthma group urinary EPX, as well as serum ECP, decreased significantly after 3 months of treatment with budesonide (116.4 to 68.4 micrograms/mmol creatinine [p = 0.005] and 37.0 to 24.0 micrograms/L [p = 0.04]). At the same time, peak expiratory flow values increased significantly in the children with asthma (76.0% to 87.8% of predicted value [p = 0.005]) but not in the control subjects (87.0% to 90.1%). In the asthma group the levels of myeloperoxidase were similar to those in the control group, both at inclusion and after 3 months. CONCLUSION: Increased urinary EPX and serum ECP levels seem to reflect active atopic asthma, whereas decreased levels after antiinflammatory treatment probably reflect normalization of airway inflammation, and indirectly, improved lung function.

Adolescent↗
PubMed1996

Histaminergic regulation of interferon-gamma (IFN-gamma) production by human natural killer (NK) cells.

Monocytes, recovered from human peripheral blood by counter-current centrifugal elutriation, effectively inhibit the production of IFN-gamma by CD3-/56+ NK cells in response to IL-2. This study aimed at defining the nature of the inhibitory signal, particularly the importance of monocyte-derived reactive metabolites of oxygen. It was found that monocytes recovered from patients with chronic granulomatous disease (CGD), a condition characterized by deficient NADPH-oxidase activity of phagocytes, did not inhibit IFN-gamma production by NK cells. Further, catalase, a scavenger of hydrogen peroxide, completely reversed the inhibitory signal whereas scavengers of the superoxide anion, hypohalous acids, the hydroxyl radical, or nitric oxide synthesis inhibitors such as L-NMMA were ineffective. Inhibition of IFN-gamma production was operating on a pretranslational level, as indicated by the inability of enriched NK cells to accumulate IFN-gamma mRNA in the presence of elutriated monocytes. Hydrogen peroxide, at micromolar concentrations, reconstituted the inhibition of IFN-gamma production when added to enriched NK cells. Histamine, a biogenic amine which inhibits the generation of reactive oxygen metabolites in monocytes, abrogated the inhibition of IFN-gamma production in NK cells; by this mechanism, histamine strongly synergized with IL-2 to induce IFN-gamma in mixtures of NK cells and monocytes. The synergizing effect of histamine was specifically mediated by H2-type histamine receptors. We conclude that: (i) the induction of IFN-gamma mRNA in NK cells is effectively down-regulated by products of the oxidative metabolism of monocytes; and (ii) histamine effectively enhances IFN-gamma production by preventing monocyte-induced oxidative damage to NK cells.

Base Sequence↗
PubMed1996

A study of the cellular immune response to enteroviruses in humans: identification of cross-reactive T cell epitopes on the structural proteins of enteroviruses.

We have attempted to extend our understanding of the enteroviral cross-reactive T cell response in humans. Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated in vitro with six different serotypes of enterovirus and 15 synthetic peptides representing conserved regions in the four structural proteins of these viruses. Upon challenge with different antigens, PBMC from donors responded specifically with proliferation and production of interferon-gamma (IFN-gamma). In contrast, synthesis of interleukin-4 (IL-4) or IL-10 was not detected. A T cell response to each enterovirus serotype was recorded in all individuals even though not all individuals had serum neutralizing antibody against each virus. These data confirmed previous findings that human T cells recognize enteroviral cross-reactive epitopes. Analysis of the peptide-induced IFN-gamma production and proliferative response showed that the cross-reactive T cell epitopes are localized mainly in capsid protein VP2 and VP3 and to a lesser extent in VP1. Surprisingly, T cell epitopes were not identified in the most conserved structural protein of enterovirus, VP4. Immune responses were mediated by CD4+ T cells in association with MHC class II molecules. The sources of IFN-gamma in response to the most immunodominant cross-reactive T cell epitopes were CD4+, CD8+ and NK cells. The two latter subsets produced IFN-gamma provided CD4+ T cells were present. Since T helper 1 (Th1) cells can mediate an in vivo protective immune response against poliovirus infection in mice, our novel findings in humans merit further detailed characterization of T cells that recognize the enteroviral cross-reactive T cell epitopes.

Amino Acid Sequence↗
PubMed1994

Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis.

Sequential samples of serum and cerebrospinal fluid (CSF), from 9 patients with herpes simplex encephalitis (HSE), were analyzed for cytokines and soluble cytokine receptors. The response to herpes simplex virus was characterized by a vigorous compartmentalized immune response. The intrathecal response comprised three different phases: an acute stage (first week of illness), characterized by elevated CSF levels of interleukin (IL)-6 and interferon-gamma; an early convalescence stage (weeks 2-6 after onset of disease), associated with peaking levels of tumor necrosis factor-alpha and late markers of the specific T cell-mediated immune response, soluble IL-2 receptor, and soluble CD8 antigen (sCD8); and finally, a late convalescence stage, lasting months to years and associated with persistently increased levels of sCD8 in particular. These findings show the compartmentalization and kinetics of the inflammatory response in HSE and demonstrate persistence of the intrathecal inflammatory process, which may have implications for antiviral and antiinflammatory therapy.

Adult↗
PubMed1994

Eosinophil cationic protein in nasopharyngeal secretions and serum of infants infected with respiratory syncytial virus.

Eosinophil cationic protein (ECP) was assayed in nasopharyngeal secretion (NPS) and serum from 42 infants, hospitalized with acute lower respiratory infection, in El Salvador and the results analyzed in relation to etiology of the infection. ECP concentrations were high in NPS, at an average 50 times higher than those found in serum. Exceedingly high levels of ECP (> 1000 micrograms/L) were found more frequently in wheezing than in non-wheezing children (30% vs 7%) and, accordingly, were more commonly found in children hospitalized with bronchiolitis than in those with pneumonia. Excessive levels were significantly more common in girls than in boys. Of the 42 cases, 28 were found to be caused by respiratory syncytial virus (RSV) subgroup A, and 3 by RSV-B, by means of detection of RSV antigen in nasopharyngeal cells. ECP serum levels were moderately elevated during the acute phase of the respiratory infection and increased slightly but significantly, in cases with RSV antigen-positive bronchiolitis, but not in those with pneumonia. The ECP levels in NPS from patients in Sweden who, by antigen detection in NPS cells, were diagnosed as either RSV or para-influenza 3 infection or none of these, were similar. These results indicate that elevation of ECP in NPS is associated with acute lower respiratory infection in general, but particularly pronounced in cases of bronchiolitis. Elevation of ECP is not an exclusive consequence of RSV infection, but may occur to an equal extent in infections caused by other agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗