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Biomedical subjects

M Schultzberg

Publications and source records attributed to M Schultzberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of peripheral administration of LPS on the expression of immunoreactive interleukin-1 alpha, beta, and receptor antagonist in rat brain.

The cytokine interleukin-1 (IL-1) appears to play a pivotal role in the orchestration of brain-mediated, nonspecific illness symptoms during an infection. In the present study, we examine the possibility that IL-1 is produced in the central nervous system itself, which may be responsible for the induction of brain-mediated responses. Using immunocytochemical techniques, we demonstrated that peripheral administration of bacterial endotoxin to rats caused a time- (1.5-24 hr) and dose-dependent (4 micrograms/kg-2.5 mg/kg) induction of IL 1 beta immunoreactivity in cells identified as macrophages in meninges and choroid plexus and microglial cells in various brain regions. At 8 hr after endotoxin (2.5 mg/kg), immunoreactive IL-1 alpha was observed in the same areas and cell types as IL-1 beta. Although no quantitative measurements have been performed, it appears that fewer cells express immunoreactive IL-1 alpha than IL-1 beta. Furthermore, IL-1ra was found to be constitutively expressed in neurons in the paraventricular nucleus and supraoptic nucleus, which is in accordance with mRNA data. After administration of endotoxin, we observed no additional cells that expressed immunoreactive IL-1ra. We conclude that IL-1 alpha and IL-1 beta production in the brain is induced in the same cell types, whereas IL-1ra is expressed constitutively by a different cell type--probably neurons.

Animals↗
PubMed1997

Colocalization of somatostatin- and HLA-DR-like immunoreactivity in dendritic cells of psoriatic skin.

This study presents an immunohistochemical characterization of somatostatin-positive dendritic cells in psoriatic lesions. Somatostatin is a neuropeptide with inhibitory action on several neuropeptides and hormones, but also with immunomodulating properties, and has been used in several studies as treatment for psoriasis. The number of somatostatin-positive dendritic cells was found to be larger in psoriatic lesions than in normal skin of psoriasis patients and healthy controls. Colocalization of somatostatin and HLA-DR immunoreactivity was demonstrated in a subgroup of dendritic cells of psoriatic skin, whereas double-labelled cells were not found in uninvolved skin. The somatostatin-positive cells in the epidermis and dermis did not co-express CD1a, CD35, CD45RB, CD45RO, CD68, factor XIIIa or S-100. On the basis of these findings, the somatostatin-positive cells seem to represent a specific population of dermal dendritic cells, distinct from Langerhans' cells and factor XIIIa-positive cells, which are found in elevated amounts in chronic plaque psoriasis.

Adult↗
PubMed1996

Regionally specific induction of ICE mRNA and enzyme activity in the rat brain and adrenal gland by LPS.

Pro interleukin-1 beta converting enzyme (ICE) activity in the pituitary was found to be significantly increased 4 h after intraperitoneal injection of E. coli lipopolysaccharides, when distribution and inducibility of the enzyme was studied in the adult rat brain and the adrenal gland, using an artificial fluorescence peptide substrate. The same lipopolysaccharide treatment induced ICE mRNA levels in the pituitary, adrenal gland and hypothalamus as studied by reverse transcript-polymerase chain reaction.

Adrenal Glands↗
PubMed1996

Proinflammatory cytokines and their corresponding receptor proteins in eccrine sweat glands in normal and cutaneous leishmaniasis human skin. An immunohistochemical study.

Paraformaldehyde-fixed biopsy specimens of normal and chronic cutaneous leishmaniasis human skin were investigated for the presence and cellular distribution of interleukin-1 alpha, interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and the corresponding receptors in eccrine sweat glands, using an indirect immunoperoxidase technique. There was cytoplasmic staining for all 4 cytokines as well as their receptor proteins in the clear cells of the eccrine sweat glands of both normal and inflamed skin specimens. No staining could be seen in the dark cells or the myoepithelial cells, neither in normal nor in inflamed skin. However, a difference between normal and inflamed skin was observed in the ductal system. Thus, cell layers of the dermal ducts in leishmaniasis skin were stained for all 4 cytokines, with more intense labelling in the basal cell layer of the coiled ducts, while in the normal skin, an intense staining was more evident in the inner luminal layer, with variable and less intense labelling of the basal layer. The immunolabelling for the cytokine receptors within the dermal ducts exhibited similar staining intensity in both luminal and basal cell layers, except in the case of the IL-6 receptor, which showed a moderate to intense signal in the basal cell layer but a weak staining of the luminal cell layer. Infiltrating inflammatory cells around the sweat gland apparatus in leishmaniasis skin exhibited immunoreactivities for all cytokines and their corresponding receptors.

Adult↗
PubMed1996

Immunohistochemical studies of proinflammatory cytokines and their receptors in hair follicles of normal human skin.

Immunoreactivity to interleukin-1 alpha, interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and their receptors, as well as the endogenous interleukin-1 receptor antagonist, was investigated in hair follicles in paraffin-embedded normal human skin. Interleukin-1 beta- and tumour necrosis factor-alpha-like immunoreactivities were found in the inner root sheath layer of hair follicles, at the suprapapillary level. Interleukin-1 receptor-like immunoreactivity was also found in this layer, while there was a variable immunoreactivity to the interleukin-1 receptor antagonist. In the outer root sheath there was a weak to moderate staining for the four cytokines, in addition to intense staining for their receptors and a weak staining for the antagonist. The fibrous root sheath had a moderate immunoreactivity for interleukin-1 alpha and interleukin-6. The distribution patterns suggest that these cytokines, particularly interleukin-1 beta and tumour necrosis factor-alpha, may have a protective role in hair formation, while all the investigated proinflammatory cytokines may have a role in the differentiation process.

Adult↗
PubMed1995

Capsaicin effects on substance P and CGRP in rat adjuvant arthritis.

The effects of capsaicin on the sensory neuropeptides substance P and calcitonin gene-related peptide were analyzed in the ankle joints and dorsal root ganglia (L2-L6) of adult female Lewis rats. The study included 23 normal rats and 23 arthritic rats, all injected subcutaneously with capsaicin (total dose 200 mg/kg bw). Another two groups of animals from a previous study, i.e., 23 normal rats and 23 arthritic rats not given capsaicin served as controls. Adjuvant arthritis was induced by inoculation with heat-killed mycobacteria. The morphological distribution of sensory neuropeptides was assessed by immunohistochemistry and the tissue concentrations were determined by radioimmunoassay. In normal rats, capsaicin significantly reduced the concentrations of substance P and calcitonin gene-related peptide in ankle joints (54 and 36%, respectively) as well as dorsal root ganglia (40 and 54%, respectively). In arthritic rats those pretreated with capsaicin had significantly lower concentrations of substance P and calcitonin gene-related peptide in dorsal root ganglia (19 and 42%, respectively) compared to the arthritic controls. In the ankle joints, however, only the SP concentration was reduced (42%). Notably, this was accompanied by a 40% reduction in inflammatory response as assessed by comparing the ankle joint weights of the experimental groups. In general, there was a good correlation between the neuropeptide concentrations in ipsilateral ankle joints and the corresponding dorsal root ganglia as assessed in individual rats. The present study of adjuvant induced arthritis shows that capsaicin administration reduces the otherwise up-regulated levels of sensory neuropeptides in dorsal root ganglia and ankle joints. However, capsaicin at the dose given can only mitigate, not completely prevent the development of joint inflammation. Nonetheless, the findings suggest that antineuronal therapy targeted against specific neurotransmitters may prove useful in inflammatory joint disease.

Animals↗
PubMed1995

Increased levels of substance P and calcitonin gene-related peptide in rat adjuvant arthritis. A combined immunohistochemical and radioimmunoassay analysis.

OBJECTIVE: To analyze the occurrence of substance P (SP) and calcitonin gene-related peptide (CGRP) in ankle joints and corresponding dorsal root ganglia (L2-L6) of rats with adjuvant arthritis. METHODS: Arthritis was induced by inoculation with heat-killed mycobacteria. The morphologic distribution of SP and CGRP was assessed by immunohistochemical analysis. Tissue concentrations of the neuropeptides were determined by radioimmunoassay. RESULTS: Neuronal CGRP-like immunoreactivity was clearly increased in the synovium and the dorsal root ganglia, whereas the increase in SP-positive structures was less pronounced. The tissue concentrations of SP and CGRP were significantly increased both in ankle joints and in dorsal root ganglia. CONCLUSION: Levels of sensory neuropeptides are increased under conditions of joint inflammation.

Animals↗
PubMed1995

Neuropeptide Y- and vasoactive intestinal polypeptide-like immunoreactivity in adjuvant arthritis: effects of capsaicin treatment.

The occurrence of the neuropeptides vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in ankle joints and dorsal root ganglia (L2-L6) was analyzed in normal and arthritic Lewis rats. In addition the effect of capsaicin pretreatment was investigated. The study included 92 rats consisting of 4 groups, 23 rats in each; normal rats, normal rats given capsaicin, arthritic rats and arthritic rats pretreated with capsaicin. The localization of the neuropeptides was assessed by immunohistochemistry and the tissue concentrations were determined by radioimmunoassay (RIA). In the arthritic rats, there was a slight increase in NPY immunoreactive nerve fibres in the ankle joint synovium and bone marrow, as compared to normal rats. Notably, there was an intense fluorescence and significant increase (p < 0.01, 41%) in the number of NPY-positive megakaryocytes in the tibial bone marrow of arthritic rats. RIA showed that the concentration of NPY-like immunoreactivity (LI) was increased by 50% in the ankle joint. Pretreatment with capsaicin did not affect the increased level of NPY-LI in the ankle joint of arthritic rats. The concentration of NPY-LI in the dorsal root ganglia was not altered in arthritic rats, nor was it affected by the capsaicin treatment. No NPY immunoreactive cells could be detected in the dorsal root ganglia. The number of VIP immunoreactive nerve fibres observed in ankle joints of arthritic and normal rats did not differ. However, RIA measurements showed an 11% increase in the VIP concentration in arthritic rats, which was unaffected by capsaicin treatment. In dorsal root ganglia, RIA disclosed a 21% increase in VIP-LI, although no VIP-positive cells could be detected. Capsaicin treatment did not affect the increased concentration of VIP-LI in the dorsal root ganglia.

Animals↗
PubMed1995

Effects of surgical denervation on substance P and calcitonin gene-related peptide in adjuvant arthritis.

The occurrence of substance P (SP) and calcitonin gene-related peptide (CGRP) was assessed in the ankle joints and dorsal root ganglia (L2-L6) by immunohistochemistry and radioimmunoassay (RIA) after unilateral sciatic nerve section in adjuvant arthritis. Nerve section in arthritic rats had no clear-cut effect on warmth, redness, and swelling of ankle joints, but significantly affected the occurrence of SP and CGRP. Immunohistochemical analysis showed an almost complete disappearance of SP-positive fibers in the ipsilateral ankle joint in normal rats after axotomy, whereas in arthritic rats occasional SP-positive fibers remained. In dorsal root ganglia, only occasional SP-positive cells could be detected in normal and arthritic rats after axotomy. A similar but somewhat less pronounced effect of axotomy was noted for neuronal CGRP-LI. RIA showed a decrease in SP in ankle joints by 45% in normal rats and 58% in arthritic rats; the decrease in CGRP was 41% and 47%, respectively. In dorsal root ganglia, the decrease in SP after surgical denervation was 25% in normal rats and 54% in arthritic rats; the decrease in CGRP was 18% and 27%, respectively. The tissue concentrations of SP and CGRP in ipsilateral ankle joints and dorsal root ganglia were consistently correlated in normal as well as arthritic rats. The present study shows that an interruption of the nerve supply to joints cannot fully prevent the development of arthritis, although it significantly reduces the occurrence of sensory neuropeptides.

Animals↗
PubMed1995

Interleukin-1 immunoreactive nerves in heterotopic bone induced by DBM.

The occurrence of interleukin-1-positive nerves was investigated by immunohistochemistry in developing heterotopic bone, induced by demineralized allogeneic bone matrix (DBM) in the rat. Interleukin-1 immunoreactivity was observed 1 week after implantation and remained until the end of the experiment at 12 weeks. Immunoreactive material was first identified in mononuclear cells at day 7. Interleukin-1 immunoreactive nerve fibers were first observed in the fibrous tissue at 2 weeks after implantation. A maximum density of fibers was reached at 8 weeks. Abundant immunofluorescent fibers were observed in the marrow tissue of the ossicles, and also in the surrounding fibrous tissue. A substantial number were vascular, but in the bone marrow most of the nerve fibers appeared as irregularly arranged, non-vascular terminals with ramifications and varicosities, intermingled between the marrow cells. No fibers could be detected in the proper bone tissue. The distribution of interleukin-1-positive nerves in the ossicles strongly resembled that previously observed in rat long bones. Moreover, the shape and distribution of the fibers exhibited a striking similarity to that of noradrenergic fibers identified previously both in ossicles and normal rat long bones. The late occurrence and predominant distribution in marrow tissue would seem to imply that neuronal interleukin-1 does not participate in the early differentiation of bone cells. The most important finding seems to be the presence of interleukin-1-positive nerve terminals in blood vessel walls and amidst marrow cells.

Animals↗
PubMed1995

Interleukin-1 receptor antagonist protein and mRNA in the rat adrenal gland.

The occurrence of the endogenous receptor antagonist for the cytokine interleukin-1 in the rat adrenal gland was analyzed y polymerase chain reaction and by immunohistochemistry using a rabbit polyclonal antiserum. Expression of interleukin-1 receptor antagonist mRNA was demonstrated in both adrenal medulla and cortex, and a marked increase in the transcription was observed after systemic administration of lipopolysaccharides. Interleukin-1 receptor antagonist immunoreactivity was seen in the adrenal medulla, and the immunofluorescence intensity was stronger in the adrenergic, phenylethanolamine N-methyltransferase-positive cells than in the noradrenergic chromaffin cells. The distribution of interleukin-1 receptor antagonist protein is complementary to that of interleukin-1 alpha-like immunoreactivity found in phenylethanolamine N-methyltransferase-negative cells and overlaps with and resembles the distribution of interleukin-1 beta-immunoreactive material. The expression of the interleukin-1 receptor antagonist in the adrenal gland complements previous findings of large constitutive pools of interleukin-1 alpha and interleukin-1 beta in this neuroendocrine organ and also suggests participation of adrenal interleukin-1 receptor antagonist in neuroimmune modulation.

Adrenal Medulla↗
PubMed1995

Interleukin (IL)-1 alpha- and -1 beta-, IL-6-, and tumor necrosis factor-alpha-like immunoreactivities in human common and dysplastic nevocellular nevi and malignant melanoma.

Interleukin-1 alpha and -1 beta, interleukin-6, and tumor necrosis factor-alpha may have a protective effect against malignant transformation of melanocytes. By using monoclonal and polyclonal antisera we investigated, in paraformaldehyde-fixed tissue, the cellular distribution of these cytokines in human common and dysplastic nevocellular nevi and in malignant melanoma. Generally, the immunolabeling for all of these cytokines was both cytoplasmic and perinuclear as well as present in the basement membrane, which surrounds the individual cells or cellular nests of some of the nevi. In compound and intradermal nevi the immunolabeling was abundant, although there was a variation in the staining intensity between individual cells and even inside a single nevus cell, ranging from weak to strong. There was a strong labeling of the basement membrane around the cellular nests and around individual cells inside or outside the nests in the papillary and reticular dermis. With regard to the common junctional and dysplastic nevi and malignant melanoma, occasional immunolabeling could be seen in some cells within the cellular nests in the junctional area or papillary dermis, ranging from faint to moderate in intensity, but in this case the basement membrane around individual cells or cellular nests was not stained. The staining of nevocellular nevi and malignant melanoma indicates the possibility of these cytokines being synthesized by the nevi and melanoma cells. The labeling of the basement membrane in compound and intradermal nevi suggests that cytokines produced by nevocellular cells may be stored in the basement membrane, from which they could be released upon environmental or mechanical challenge. This distribution pattern would support the hypothesis that these cytokines may protect the common nevi from malignant transformation.

Basement Membrane↗
PubMed1994

Interleukin-1 alpha- and beta-, interleukin-6- and tumour necrosis factor-alpha-like immunoreactivities in chronic granulomatous skin conditions.

Paraformaldehyde-fixed tissue of chronic granulomatous skin conditions, such as cutaneous leishmaniasis, granuloma annulare, leprosy and hidroadenitis, was investigated for the presence of interleukin-1 alpha-, interleukin-1 beta-, interleukin-6- and tumour necrosis factor-alpha-like immunoreactivities among the cellular infiltrates. There was a weak to strong cytoplasmic labelling of plasma cells for interleukin-6 and tumour necrosis factor-alpha at the periphery of the granulomatous mass and around the skin appendages. The interleukin-6-like immunoreactivity seemed to be correlated with the coarseness of the chromatin material of the cells, being more intense with coarse chromatin. The cytoplasmic labelling for interleukin-1 alpha and interleukin-1 beta in the plasma cells was less intense. Epitheloid, Langhans' giant cells and small round cells exhibited a weak to moderate cytoplasmic labelling for interleukin-1 alpha and interleukin-1 beta, whereas the staining intensity for interleukin-6 and tumour necrosis factor-alpha was weak to strong. In addition, there was staining of the stroma in the centre of granuloma with antisera against interleukin-1 alpha, interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha. This area contained few cells, suggesting that the granuloma was in a resolution process. A contribution of interleukin-6 and tumour necrosis factor-alpha to the granulomatous reaction, at least during the maintenance period, is suggested by the occurrence of these cytokines in the skin conditions studied. The findings are also consistent with a suggested role of B cells in the late stages of the granulomatous reaction. In addition, they are in line with the reported declining role of interleukin-1 in the maintenance of granuloma.

Chromatin↗
PubMed1993

Sensory and autonomic innervation of the facet joint in the rat lumbar spine.

The presence of sensory and autonomic nerves in the synovial membrane of the lumbar facet joint in rats was investigated by immunohistochemistry. Substance P and calcitonin gene-related peptide immunoreactivities, representing sensory nerves, were observed as varicose fibers in the synoviocyte layer. The fibers were predominantly nonvascular. The autonomic innervation was identified by the presence of neuropeptide Y- and tyrosine hydroxylase-positive fibers. Most of these fibers were found adjacent to or within blood vessel walls. Immunoreactivity to vasoactive intestinal polypeptide was seen in varicose nerve terminals in the synoviocyte layer, mostly unrelated to blood vessels. There is accumulating evidence of an involvement of both the sensory and sympathetic nervous systems in inflammatory joint disease. The neuropeptides now identified in lumbar facet joints may prove to play a significant role in the pathogenesis of low-back pain.

Animals↗
PubMed1993

Cytokines in neuronal cell types.

Cytokines are signals in the immune system, and may have effects on cells distant from the cells of origin. These proteins have been suggested as messengers in the communication between the immune system and the nervous system, in which signals travel only short distances. Neuroimmune interactions have been discussed in view of findings that nervous signals are important for the immune response. The occurrence of neurotransmitter receptors on lymphocytes and cytokine receptors on nerve cells or glia has initiated further studies e.g. on the localization of different cytokines in the nervous system and on long and short term actions of cytokines in the nervous system. Interleukin-1 has been studied extensively along these lines, and found to occur in the nervous and endocrine system, for example in the adrenal chromaffin cells, and to have effects such as induction of slow-wave sleep and stimulation of adrenocortical and gonadotropic hormones. Other cytokines implicated as signals in neuroimmune interactions are IL-2, IL-6, IFN-gamma and TNF-alpha. The functional studies suggest the occurrence of cytokine receptors in the brain, and experiments using 125iodine-labelled IL-1 alpha demonstrate differential distribution of binding sites in the mouse brain. Recently, evidence emerged of an endogenous receptor antagonist for IL-1, which may prove useful for the understanding of the mechanisms of IL-1's actions in the nervous system. A role for cytokines in regulation of the immune response but also in adjusting the organism to the host reaction is implicated. Furthermore, several findings indicate their role as growth promoting factors, and for example the induction of NGF production by IL-1 suggests involvement of this cytokine in regeneration and development in the nervous system. The significance of neuronally produced cytokines may be based upon the anatomically distinct releasing sites that the specific synaptic organization of the nervous system offer and future studies should determine whether cytokines act as neurotransmitters.

Animals↗
PubMed1993

Neuropeptide Y, tyrosine hydroxylase and vasoactive intestinal polypeptide-immunoreactive nerve fibers in the vertebral bodies, discs, dura mater, and spinal ligaments of the rat lumbar spine.

The occurrence of autonomic nerves in the lumbar spine of rats was investigated by immunohistochemical technique. Both peptidergic nerves, represented by immunoreactivity to neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and noradrenergic nerves as reflected by tyrosine hydroxylase (TH) immunoreactivity, were identified. NPY- and TH-positive nerves were predominantly found in the blood vessels walls. They occurred in the bone and periosteum of the vertebral body, disc, dura mater, and in the spinal ligaments. They were particularly numerous along the growth plate and in the outer layers of the intervertebral discs. VIP-positive fibers were predominantly nonvascular. They occurred in all tissues analyzed, but were most abundant in the vertebral bone marrow and periosteum. The VIP-immunoreactive fibers in the outer fibrous layers of the disc and the spinal ligaments were occasionally observed in blood vessel walls. No immunoreactivity could be detected in the nucleus pulposus. In the dura mater, NPY-, TH- and VIP-positive fibers were found both in the ventral and dorsal portion. In view of the vasoconstrictive properties of both NPY and noradrenaline, it may be assumed that the abundance of NPY- and TH-immunoreactive nerves fibers in blood vessel walls reflects a vasoregulatory activity. The predominance of nonvascular VIP-positive fibers in the vertebral bone marrow and periosteum may represent an involvement in local bone physiology.

Animals↗
PubMed1993

A decomposition product of a contaminant implicated in L-tryptophan eosinophilia myalgia syndrome affects spinal cord neuronal cell death and survival through stereospecific, maturation and partly interleukin-1-dependent mechanisms.

The L-tryptophan eosinophilia myalgia syndrome (L-TRP-EMS), an inflammatory syndrome characterized by eosinophilia, myalgias, perimyositis, fasciitis and neuropathies, occurred in epidemic proportions in the United States in the summer and fall of 1989. The neuropathic clinical features in L-TRP EMS are complex and mixed. In the present study, one of the impurities most highly associated with development of L-TRP EMS, 1,1'-ethylidenebis[L-tryptophan] (EBT), and two of its diastereoisomeric breakdown products, were compared for evidence of neurotoxicity in vitro. In 1-month-old spinal cord cultures derived from fetal mice, synthetic (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (1S-beta-C) produced a 30 to 35% loss in numbers of neurons. Toxicity was not apparent after treatment with the R-isomer of the same compound or with the parent compound, EBT. Cotreatment of cultures with 1S-beta-C and neutralizing antiserum to interleukin-1 alpha (IL-1 alpha), or with 1S-beta-C and neutralizing antiserum against the murine IL-1 receptor, prevented neuronal cell death associated with 1S-beta-C. Recombinant IL-1 alpha also produced neuronal killing that was not additive to that observed with the 1S-beta-C treatment. In contrast, in immature spinal cord neuronal cultures, the 1S-beta-C, but not the 1R-beta-C or EBT, prevented the 30% cell death which normally occurs in these cultures. Neither neutralizing anti-IL-1 antibody, nor anti-IL-1 receptor antibody blocked the neuronal survival effect, suggesting that 1S-beta-C induces neuronal survival through a receptor-mediated mechanism independent of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗