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T Olsson

Publications and source records attributed to T Olsson.

At least 163 records · Page 9Linked to original sources
PubMed1996

The length of treatment determines whether IFN-beta prevents or aggravates experimental autoimmune encephalomyelitis in Lewis rats.

The mechanism of action underlying the beneficial effect of IFN-beta in multiple sclerosis (MS) is not understood. To date, little information is available on the effects of IFN-beta in experimental autoimmune encephalomyelitis (EAE), the animal correlate of the human disease MS. Therefore, we investigated the effects of recombinant rat IFN-beta (rrIFN-beta) on EAE in Lewis rats with emphasis on a treatment regimen during the paralytic phase of the disease. The results indicated that rrIFN-beta dose-dependently inhibited disease activity with complete prevention at a s.c. dose of 300,000 U/day, provided that treatment was continued for 3 wk. Discontinuation of treatment on day 17 postimmunization resulted in a protracted and relapsing disease course with strongly enhanced clinical severity. Detailed immunohistology of central nervous system (CNS) tissue of protected animals revealed an almost complete absence of CNS lesions and a >90% reduction in the number of infiltrating leukocytes. Accordingly, isolation of mononuclear cells from spinal cord tissue of successfully treated EAE rats revealed a reduction of approximately 95% in the number of cells that produce IFN-gamma in response to the encephalitogenic peptide MBP63-88. Furthermore, rrIFN-beta significantly enhanced serum corticosterone levels, which showed an inverse relationship with disease activity. We show that rrIFN-beta can have both beneficial and detrimental effects on disease activity dependent on the timing and the duration of treatment. Beneficial effects on EAE are associated with inhibition of the extravasation of blood-derived mononuclear cells in the CNS.

Animals↗
PubMed1996

Control of parasitemia and survival during Trypanosoma brucei brucei infection is related to strain-dependent ability to produce IL-4.

We studied non-MHC gene-dependent expression of a number of cytokines in relation to host defense and survival during Trypanosoma brucei brucei (Tbb) infection in mice. In particular, the role of IL-4 was explored with use of genomically IL-4-disrupted mice and in vivo Ab blocking. Splenocytes from MHC-identical B10.Q (relatively resistant) mice showed day 5 postinfection higher numbers of IL-4 mRNA expressing cells than C3H.Q (highly susceptible). A trypanosome-derived lymphocyte triggering factor, which is released by Tbb to polyclonally activate CD8+ T cells, stimulated naive splenocytes in vitro to a higher IL-4 response in B10.Q than in C3H.Q mice. The C3H.Q mice developed an extremely high parasitemia, showed a low Ab response against the variant surface glycoprotein (VSG), and had a mean survival time of 42 days. Conversely, B10.Q mice had lower parasitemia, mounted higher anti-VSG response, and had a mean survival time of 56 days. Deletion of the IL-4 gene had no influence on the infection in C3H.Q mice, while in B10.Q mice the deletion was associated with lower anti-VSG Ab levels and higher parasitemia. Paradoxically, B10.Q mice with disrupted IL-4 gene survived longer than the wild type. Anti-IL-4 Ab-blocking experiments in vivo displayed an enhanced parasitemia and prolonged survival in infected B10.Q mice. We conclude that 1) a non-MHC gene-related and CD8+-dependent ability to produce IL-4 partly determines the susceptibility to Tbb infection; and 2) IL-4, although involved in controlling the levels of parasitemia by its effects on immunoglobulin synthesis, also can have toxic effects on the animals.

Animals↗
PubMed1996

Both CD4+ and CD8+ T cells are essential to induce experimental autoimmune myasthenia gravis.

CD4+ T cells have been shown to be crucial in the development of experimental autoimmune myasthenia gravis (EAMG). The role of CD8+ T cells in EAMG is less well established. We previously showed that antibody depletion of CD8+ T cells in rats effectively suppresses EAMG. To further study the role and relationship of CD4+ versus CD8+ T cells in induction of EAMG, CD4-/-, CD8-/-, and CD4-8- mutant C57BL/6 mice and the parent CD4+8- wild-type mice were immunized with Torpedo acetylcholine receptor (AChR) plus complete Freund's adjuvant. Clinical EAMG was nearly completely prevented in CD4-8-, CD4-/-, and CD8-/- mice. This was associated with strongly reduced AChR-specific T and B cell responses, and with reduced levels of AChR-reactive interferon gamma (IFN-gamma) and interleukin 4 (IL-4) mRNA-expressing cells in lymphoid organs when compared with CD4+8+ wild-type mice. We conclude that (a) both CD4+ and CD8+ T cells are essential for development of EAMG, and a collaboration between these cell types may be necessary; (b) CD4+ as well as CD8+ T cells secrete IFN-gamma and IL-4, and both cytokines are involved in the development of EAMG; and (c), besides T cells, other immune cells might also be responsible for help of anti-AChR antibody production.

Animals↗
PubMed1996

Treatment of experimental autoimmune encephalomyelitis by feeding myelin basic protein conjugated to cholera toxin B subunit.

Oral administration of autoantigens can prevent and partially suppress autoimmune diseases in a number of experimental models, Depending on the dose of antigen fed, this approach appears to involve distinct yet reversible and short-lasting mechanisms (anergy/deletion and suppression) and usually requires repeated feeding of large (suppression) to massive (anergy/deletion) amounts of autoantigens to be effective. Most importantly, this approach is relatively less effective in animals already systemically sensitized to the fed antigen, such as in animals already harboring autoreactive T cells and, thus, presumably also in humans suffering from an autoimmune disorder. We have previously shown that feeding a single dose of minute amounts of antigens conjugated to cholera toxin B subunit (CTB) can effectively suppress delayed-type hypersensitivity reactions in systemically immune animals. We now report that feeding small amounts of myelin basic protein (MBP) conjugated to CTB either before or after disease induction protected rats from experimental autoimmune encephalomyelitis. Such treatment was as effective in suppressing interleukin 2 production and proliferative responses of lymph node cells to MBP as treatment involving repeated feeding with much larger (50- to 100-fold) doses of free MBP. Different from the latter treatment, which led to decreased production of interferon-gamma in lymph nodes, low-dose oral CTB-MBP treatment was associated with increased interferon-gamma production. Most importantly, low-dose oral CTB-MBP treatment greatly reduced the level of leukocyte infiltration into spinal cord tissue compared with treatment with repeated feeding of large doses of MBP. These results suggest that the protection from experimental autoimmune encephalomyelitis achieved by feeding CTB-conjugated myelin autoantigen involves immunomodulating mechanisms that are distinct from those implicated by conventional protocols of oral tolerance induction.

Animals↗
PubMed1996

Blunted adrenocorticotropin and increased adrenal steroid response to human corticotropin-releasing hormone in Alzheimer's disease.

Previous studies suggest disturbances in the central regulation of the hypothalamic-pituitary-adrenocortical axis (HPA) in advanced Alzheimer's disease (AD). In this study the reactivity of the HPA axis was evaluated by stimulation with corticotropin-releasing hormone (CRH) of patients with mild to moderate AD. Twenty-three patients with AD (aged 61-88 yr) and 19 healthy elderly (aged 62-84 yr) received an intravenous bolus injection of human CRH (1 microgram/kg) at 3:00 PM. CRH-stimulated plasma ACTH levels were significantly lower in AD patients, while serum cortisol, dehydroepiandrosterone, and androstenedione responses relative to the amount of ACTH released were higher in AD patients. Significant correlations were found between low basal plasma ACTH levels and temporal lobe atrophy (p=0.02) and between peak plasma ACTH levels and hippocampal atrophy (p = 0.01). These findings suggest abnormalities at several levels of HPA axis in AD.

Adrenocorticotropic Hormone↗
PubMed1996

Mucosal tolerance to experimental autoimmune myasthenia gravis is associated with down-regulation of AChR-specific IFN-gamma-expressing Th1-like cells and up-regulation of TGF-beta mRNA in mononuclear cells.

Oral and nasal administration of nicotinic acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with AChR and complete Freund's adjuvant (CFA) resulted in prevention or marked decrease of the severity of experimental autoimmune myasthenia gravis (EAMG) and suppression of AChR-specific B-cell responses and of AChR-reactive T-cell function. To examine the involvement of immunoregulatory cytokines and the underlying mechanisms involved in tolerance induction, in situ hybridization with radiolabeled cDNA oligonucleotide proves was adopted to enumerate mononuclear cells (MNC) expressing mRNA for the proinflammatory cytokine interferon-gamma (IFN-gamma), the B cell-stimulating interleukin-4 (IL-4), and the immunosuppressive transforming growth factor-beta (TGF-beta). Popliteal and inguinal lymph nodes from EAMG rats contained elevated numbers of AChR-reactive IFN-gamma, IL-4, and TGF-beta mRNA-expressing cells, compared to control rats receiving PBS orally or nasally and injected with CFA only. Oral and nasal tolerance was accompanied by decreased numbers of AChR-reactive IFN-gamma and IL-4 mRNA-expressing cells and strong up-regulation of TGF-beta mRNA-positive cells in lymphoid organs when compared to nontolerized EAMG control rats. The results suggest that IFN-gamma and IL-4 are central effector molecules in the development of EAMG and that TGF-beta plays an important role in tolerance induction to EAMG.

Administration, Intranasal↗
PubMed1996

In situ hybridization analysis of synovial and systemic cytokine messenger RNA expression in superantigen-mediated Staphylococcus aureus arthritis.

OBJECTIVE: To investigate patterns of synovial and systemic cytokine messenger RNA (mRNA) expression in mice with superantigen-mediated Staphylococcus aureus arthritis. METHODS: Mice were inoculated intravenously with 1 x 10(7) colony-forming units of toxic shock syndrome toxin-1-producing S aureus LS-1. Synovial tissues and spleens were obtained at varying time intervals after bacterial inoculation, and examined for mRNA expression of interleukin-1beta (IL-1beta), IL-4, IL-10, IL-12, tumor necrosis factor alpha (TNFalpha), TNFbeta, interferon-gamma (IFN-gamma), transforming growth factor beta, and perforin, by an in situ hybridization technique. RESULTS: In situ hybridization revealed early synovial up-regulation of TNFalpha and IL-1 beta mRNA expression. Peak frequencies of these proinflammatory cytokines were observed at the second and third week of the infection. Expression of T cell-derived cytokine mRNAs was detected later, and in a relatively low frequency. Notably, induction and peak numbers of Th2 cytokine (IL-4 and IL-10) mRNA expression preceded Th1 cytokine (IFNgamma and TNFbeta) mRNAs. In comparison with synovial tissues, peak spleen cytokine mRNA expression of IL-1beta, TNFalpha, TNFbeta, IL-12, and IFNgamma occurred earlier, but displayed a clearly lower magnitude of expression. CONCLUSION: These findings demonstrate synovial and systemic up-regulation of cytokine mRNA expression during S aureus arthritis, indicating that both monocyte/macrophage and T cell-derived products are involved in the pathogenesis of this disease.

Animals↗
PubMed1996

Human and rodent interferon-gamma as a growth factor for Trypanosoma brucei.

An example for the bidirectional exchange of activating signals between a pathogen and immunocompetent cells in the host is presented. Trypanosoma brucei, which include subspecies that cause African sleeping sickness, secrete a molecule that triggers lymphocytes to produce interferon (IFN)-gamma. We now report that proliferation of T. brucei is stimulated in axenic cultures by IFN-gamma. The growth-enhancing effect on the pathogen is inhibited by anti-IFN-gamma receptor (R) antibodies and does not occur after exposure to other cytokines, i.e. IFN-alpha, IFN-beta and tumor necrosis factor (TNF)-alpha. While rodent-pathogenic T. brucei strains are stimulated by rat IFN-gamma, human pathogenic strains are more potently stimulated by human IFN-gamma. Rat and human IFN-gamma can partially block each others effects. Mice with disrupted IFN-gamma genes have reduced parasitemia and prolonged survival, while the outcome is reversed in mice that lack the IFN-gamma R gene.

Animals↗
PubMed1996

Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis.

Memantine, a clinically employed drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rat experimental autoimmune encephalomyelitis (EAE). Interestingly, this therapeutic effect was not due to dampened CNS inflammation, as assessed by immunohistochemical evaluation of spinal cord tissue. Furthermore, numbers of interferon gamma (IFN gamma) mRNA expressing cells were not decreased, as assessed by in situ hybridization. Systemic immunity in terms of numbers of IFN gamma secreting cells in response to immunodominant myelin basic protein (MBP) peptides ex vivo was not reduced, and non-toxic doses of memantine did not affect lymphocyte proliferation or IFN gamma secretion in vitro. Considering these findings, we hypothesize that effector mechanisms responsible for reversible neurological deficits in EAE may involve NMDA receptors, and this highlights neurons as targets during autoimmune neuroinflammation.

Animals↗
PubMed1996

Different trypanozoan species possess CD8 dependent lymphocyte triggering factor-like activity.

Trypanosoma brucei brucei (T. b. brucei) release a molecule, trypanosome derived lymphocyte triggering factor (TLTF), which stimulates CD8+ cells to produce cytokines and to proliferate. We now report that T. evansi, T.b. gambiense and T.b. rhodesiense also contain factor(s) with similar activity. Thus, homogenates from these parasite taxa triggered mouse or rat lymphoid tissue of mononuclear cells (MNC) to produce interferon gamma (IFN-gamma) and to proliferate. These responses were dependent on CD8 since the activity was blocked by (a) anti CD8 antibodies, (b) occurred in CD8+ but not in CD8- mice and (c) was recorded in human CD8+ but not in CD4+ enriched peripheral blood mononuclear cells (PBL). The presence of TLTF or TLTF-like molecules in the trypanozoan species was also examined by T.b. brucei directed anti-TLTF Mabs using two Mabs with inhibitory activity and one with stimulatory activity. The lymphocyte triggering activity of T.b. gambiense and T.b. rhodesiense, but not T. evansi, was affected by the anti-TLTF Mabs. We conclude that T. evansi, T.b. rhodesiense and T.b. gambiense similar to T.b. brucei, all possess molecule(s) which CD8 dependently trigger lymphocytes. The latter three, related parasite taxa, share TLTF antibody binding epitopes.

Animals↗
PubMed1996

Cytokines in relapsing experimental autoimmune encephalomyelitis in DA rats: persistent mRNA expression of proinflammatory cytokines and absent expression of interleukin-10 and transforming growth factor-beta.

Experimental autoimmune encephalomyelitis (EAE) in rats is typically a brief and monophasic disease with sparse demyelination. However, inbred DA rats develop a demyelinating, prolonged and relapsing encephalomyelitis after immunization with rat spinal cord in incomplete Freund's adjuvant. This model enables studies of mechanisms related to chronicity and demyelination, two hallmarks of multiple sclerosis (MS). Here we have investigated, in situ, the dynamics of cytokine mRNA expression in the central nervous system (CNS) and peripheral lymphoid organs (lymph node cells and splenocytes) of diseased DA rats. We demonstrate that peripheral lymphoid cells stimulated in vitro with encephalitogenic peptides 69-87 and 87-101 of myelin basic protein responded with high mRNA expression for proinflammatory cytokines; interferon-gamma, interleukin-12 (IL-12), tumour necrosis factors alpha and beta, IL-1 beta and cytolysin. A high expression of mRNA for these proinflammatory cytokines was also observed in the CNS where it was accompanied by classical signs of inflammation such as expression of major histocompatibility complex class I and II, CD4, CD8 and IL-2 receptor. The expression of mRNA for proinflammatory cytokines was remarkably long-lasting in DA rats as compared to LEW rats which display a brief and monophasic EAE. Furthermore, mRNAs for putative immunodownmodulatory cytokines, i.e. transforming growth factor-beta (TGF-beta), IL-10 and IL-4 were almost absent in DA rats, in both the CNS and in vitro stimulated peripheral lymphoid cells, while their levels were elevated in the CNS of LEW rats during the recovery phase. We conclude that the MS-like prolonged and relapsing EAE in DA rats is associated with a prolonged production of proinflammatory cytokines and/or low or absent production of immunodownmodulatory cytokines.

Amino Acid Sequence↗
PubMed1996

Decreased NGFI-A gene expression in the hippocampus of cognitively impaired aged rats.

Hippocampal NGFI-A gene expression is increased following the induction of long-term potentiation, a form of activity-dependent synaptic plasticity that has been implicated in learning. In this study, we show a positive correlation between spatial learning and the constitutive expression of NGFI-A mRNA, selectively in CA1 pyramidal neurons. NGFI-A mRNA expression decreased with age in CA1, CA2 and neocortex. Long-term amitriptyline treatment, which improved spatial learning in young rats, had no significant effects on NGFI-A mRNA levels. Whether hippocampal NGFI-A plays a direct role in the mechanism of learning and memory remains to be determined.

Aging↗
PubMed1996

A low dose ACTH test to assess the function of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: The insulin tolerance test (ITT) has long been used to assess the hypothalamic-pituitary-adrenal axis, but may be hazardous. The standard synthetic ACTH (Synacthen) test has been advocated as a substitute but is sometimes insensitive. In this study the ITT has been compared to a low dose ACTH stimulation test (1 microg) and the standard ACTH stimulation test (250 microg). SUBJECTS: Twenty-seven subjects were studied, 24 with verified or suspected hypothalamic-pituitary disorders and three on long-term glucocorticoid therapy. DESIGN: Insulin tolerance, low dose ACTH and standard ACTH tests were performed in all patients. The ITT was performed less than 48 hours after the ACTH tests. Synacthen was administered as an intravenous bolus. MEASUREMENTS: Serum cortisol values were determined by radioimmunoassay. The peak cortisol value during ITT was compared to the cortisol levels during the ACTH tests. RESULTS: There was a highly significant correlation between peak cortisol values during ITT and cortisol levels after 20-60 minutes in the low dose ACTH test (r(s) = 0.91-0.93; P < 0.0001) and after 30 and 60 minutes in the standard ACTH test (r(s) = 0.85 and 0.89 respectively; P < 0.0001). Four patients showed discrepancies between the three tests. CONCLUSIONS: The 1-microg ACTH test follows the ITT more closely and may be more sensitive than the standard ACTH test in detecting more subtle insufficiency of the hypothalamic-pituitary-adrenal axis. The standard ACTH test and the insulin tolerance test may thus be replaced by the 1-microg ACTH test in screening for secondary cortisol insufficiency. We recommend that serum cortisol is measured before and 30 and 40 minutes after the ACTH injection.

Adult↗
PubMed1996

Induction of interferon-gamma, transforming growth factor-beta, and interleukin-4 in mouse strains with different susceptibilities to Trypanosoma brucei brucei.

A Trypanosoma brucei brucei-derived lymphocyte triggering factor (TLTF) induced CD8+ T cells to produce IFN-gamma, which in turn stimulates parasite growth. This parasite-host interaction was studied in mouse strains that are either relatively susceptible (C3H/He) or resistant (C57Bl/6J) to infection, as well as in athymic nude mice. In all mouse strains, T. b. brucei infection caused a strong induction of IFN-gamma production by spleen mononuclear cells (MNC). In vivo blocking of IFN-gamma by intraperitoneal injection of mouse monoclonal anti-IFN-gamma antibody suppressed parasite growth and increased survival of both C3H/H3 and C57Bl/6J animals, suggesting that, irrespective of strain-related disease susceptibility, IFN-gamma is a growth-promoting stimulus for T. b. brucei. Spleen MNC from noninfected mice of all strains were in vitro like-wise strongly induced to IFN-gamma production when exposed to TLTF. This suggests that CD8+ expressing T cell receptor (TCR) alpha/beta, gamma/delta-bearing T cells and NK cells may all be triggered to IFN-gamma production by TLTF. In all mouse strains, TLTF also caused an increase in the number of cells expressing mRNA for TGF-beta in vitro. However, significant triggering to IL-4 mRNA expression only occurred in the relatively disease-resistant C57Bl/6J strain. As IL-4 is required for the synthesis and class switches of immunoglobulins, which are essential host immune defenses against T. b. brucei, the degree of resistance may be related to inherent strain ability to produce IL-4 in response to TLTF.

Animals↗
PubMed1996

Augmented expression of tumour necrosis factor-alpha and lymphotoxin in mononuclear cells in multiple sclerosis and optic neuritis.

The involvement of proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and lymphotoxin (LT) in multiple sclerosis is suggested by the parallel occurrence of these proinflammatory cytokines in acute and chronic active multiple sclerosis brain lesions. We describe the use of in situ hybridization with radiolabelled cDNA oligonucleotide probes to detect and enumerate TNF-alpha and LT mRNA expressing mononuclear cells without culture, and after culture in the presence of myelin basic protein (MBP), control antigens or without antigen. Compared with patients with aseptic meningo-encephalitis, non-inflammatory neurological diseases and healthy controls, the multiple sclerosis patients had elevated numbers of TNF-alpha and LT mRNA expressing mononuclear cells in blood when enumerated without previous culture, and also after culture with MBP. The MBP-induced upregulation of TNF-alpha and LT was major histocompatibility complex (MHC) class II molecule dependent. Tumour necrosis factor-alpha mRNA expressing mononuclear cells were further enriched in the multiple sclerosis patients' CSF. Positive correlations were observed in multiple sclerosis between TNF-alpha and LT mRNA expressing blood mononuclear cells, MBP-reactive TNF-alpha and LT mRNA expressing cells, and TNF-alpha and interferon-gamma (INF-gamma) mRNA expressing mononuclear cells. Upregulation of TNF-alpha correlated positively with exacerbation, enhanced disability and the secondary progressive phase of multiple sclerosis. Patients with optic neuritis, in many instances representing very early multiple sclerosis, had TNF-alpha and LT positive blood mononuclear cells that were elevated to the same extent as patients with clinically definite multiple sclerosis. The findings support the hypothesis that TNF-alpha and LT play a harmful role in the development of multiple sclerosis and suggest that TNF-alpha could be useful as a disease activity marker in multiple sclerosis.

Adult↗
PubMed1996

Frequency of edentulism and identification marking of removable dentures in long-term care units.

There were two aims of this study. First, the frequency of edentulism and denture wearers among 464 residents in long-term units in Göteborg, Sweden, was evaluated. Second, the dentures were examined to determine whether they were marked correctly for identification. Of the subjects, 46% were edentulous in both jaws, and 13% in one jaw. Among complete denture wearers, 47% of the patients had at least one identification-marked denture. Removable partial dentures, worn by 26 subjects, were marked to a lesser extent (32%). Since there are many edentulous people among the elderly in most parts of the world we suggest that removable dentures are marked with the patient's name or identification number.

Age Factors↗