Biomedical subjects

G Pryce

Publications and source records attributed to G Pryce.

At least 19 recordsLinked to original sources

PubMed2007

Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors.

BACKGROUND AND PURPOSE: There is increasing evidence to suggest that cannabis can ameliorate muscle-spasticity in multiple sclerosis, as was objectively shown in experimental autoimmune encephalomyelitis models. The purpose of this study was to investigate further the involvement of CB1 and CB2)cannabinoid receptors in the control of experimental spasticity. EXPERIMENTAL APPROACH: Spasticity was induced in wildtype and CB1-deficient mice following the development of relapsing, experimental autoimmune encephalomyelitis. Spastic-hindlimb stiffness was measured by the resistance to flexion against a strain gauge following the administration of CB1 and CB2 agonists. KEY RESULTS: As previously suggested, some CB2-selective agonists (RWJ400065) could inhibit spasticity. Importantly, however, the anti-spastic activity of RWJ400065 and the therapeutic effect of non-selective CB1/CB2 agonists (R(+)WIN55,212-2 and CP55, 940) was lost in spastic, CB1-deficit mice. CONCLUSIONS AND IMPLICATIONS: The CB1 receptor controls spasticity and cross-reactivity to this receptor appears to account for the therapeutic action of some CB2 agonists. As cannabinoid-induced psychoactivity is also mediated by the CB1 receptor, it will be difficult to truly dissociate the therapeutic effects from the well-known, adverse effects of cannabinoids when using cannabis as a medicine. The lack of knowledge on the true diversity of the cannabinoid system coupled with the lack of total specificity of current cannabinoid reagents makes interpretation of in vivo results difficult, if using a purely pharmacological approach. Gene knockout technology provides an important tool in target validation and indicates that the CB1 receptor is the main cannabinoid target for an anti-spastic effect.

Animals↗

PubMed2006

Immunohistochemical localization of cannabinoid type 1 and vanilloid transient receptor potential vanilloid type 1 receptors in the mouse brain.

Cannabinoid type 1 receptors and transient receptor potential vanilloid type 1 channels have been proposed to act as metabotropic and ionotropic receptors, respectively, for two classes of endogenous polyunsaturated fatty acid amides, the acylethanolamides and the acyldopamides. Furthermore, we and others have shown that functional crosstalk occurs between these two receptors when they are expressed in the same cell. Although demonstrated in sensory neurons of the dorsal root ganglia, spinal cord and myenteric neurons, co-expression of cannabinoid type 1 and transient receptor potential vanilloid type 1 has not yet been studied in the brain. In the present study, we addressed this issue by using commercially available specific antibodies whose specificity was confirmed by data obtained with brains from cannabinoid type 1(-/-) and transient receptor potential vanilloid type 1(-/-) mice. Double cannabinoid type 1/transient receptor potential vanilloid type 1 immunofluorescence and single cannabinoid type 1 or transient receptor potential vanilloid type 1 avidin-biotin complex immunohistochemistry techniques were performed and both methods used point to the same results. Cannabinoid type 1/transient receptor potential vanilloid type 1 expression was observed in the hippocampus, basal ganglia, thalamus, hypothalamus, cerebral peduncle, pontine nuclei, periaqueductal gray matter, cerebellar cortex and dentate cerebellar nucleus. In particular, in the hippocampus, cannabinoid type 1/transient receptor potential vanilloid type 1 expression was detected on cell bodies of many pyramidal neurons throughout the CA1-CA3 subfields and in the molecular layer of dentate gyrus. In the cerebellar cortex, expression of cannabinoid type 1/transient receptor potential vanilloid type 1 receptors was found surrounding soma and axons of the vast majority of Purkinje cell bodies, whose cytoplasm was found unstained for both receptors. Cannabinoid type 1 and transient receptor potential vanilloid type 1 immunoreactivity was also detected in: a) the globus pallidus and substantia nigra, in which some intensely transient receptor potential vanilloid type 1 immunopositive cell bodies were found in dense and fine cannabinoid type 1/transient receptor potential vanilloid type 1 positive and cannabinoid type 1 positive nerve fiber meshworks, respectively; b) the cytoplasm of thalamic and hypothalamic neurons; and c) some neurons of the ventral periaqueductal gray. These data support the hypothesis of a functional relationship between the two receptor types in the CNS.

Animals↗

PubMed2005

Cannabinoid-receptor 1 null mice are susceptible to neurofilament damage and caspase 3 activation.

Administered cannabinoids have been shown to ameliorate signs of CNS inflammatory disease in a number of animal models, including allergic encephalomyelitis. More recently, neuroprotective actions have been attributed to activation of the cannabinoid 1 receptor in a number of in vitro and in vivo models. One of these, chronic relapsing experimental allergic encephalomyelitis, is considered a robust analog of multiple sclerosis. In this study, spinal cord tissue from cannabinoid receptor 1 knockout mice was analyzed for neurofilament H and myelin basic protein content, as markers of neurons/axons and myelin respectively, during the course of chronic relapsing experimental allergic encephalomyelitis. Dephosphorylation of a neurofilament H epitope, immunoreactive to the SMI32 antibody, was assessed as a marker of axonal damage and levels of the endpoint cell death mediator caspase 3 were evaluated. It was found that both neurofilament and myelin basic protein levels decrease over the course of disease, indicating concomitant neuronal/axonal loss and demyelination. Loss of each marker was more severe in cannabinoid receptor 1 knockout animals. Increased SMI32 reactivity was observed as disease progressed. SMI32 reactivity was significantly increased in knockout animals over wildtype counterparts, an indication of greater axonal dephosphorylation and injury. Active caspase 3 levels were increased in all animals during disease, with knockout animals displaying highest levels, even in knockout animals prior to disease induction. These results indicate that lack of the cannabinoid receptor 1 is associated with increased caspase activation and greater loss and/or compromise of myelin and axonal/neuronal proteins. The increase of caspase 3 in knockout mice prior to disease induction indicates a latent physiological effect of the missing receptor. The data presented further strengthen the hypothesis of neuroprotection elicited via cannabinoid receptor 1 signaling.

Animals↗

PubMed2003

Quantification of neurodegeneration by measurement of brain-specific proteins.

Quantification of neurodegeneration in animal models is typically assessed by time-consuming and observer-dependent immunocytochemistry. This study aimed to investigate if newly developed ELISA techniques could provide an observer-independent, cost-effective and time-saving tool for this purpose. Neurofilament heavy chain (NfH(SM135)), astrocytic glial fibrillary acidic protein (GFAP), S100B and ferritin, markers of axonal loss, gliosis, astrocyte activation and microglial activation, respectively, were quantified in the spinal cord homogenates of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE, n=8) and controls (n=7). Levels of GFAP were found to be threefold elevated in CREAE (13 ng/mg protein) when compared to control animals (4.5 ng/mg protein, p<0.001). The inverse was observed for NfH(SM135) (21 ng/mg protein vs. 63 ng/mg protein, p<0.001), ferritin (542 ng/mg protein vs. 858 ng/mg protein, p<0.001) and S100B (786 ng/mg protein vs. 2080 ng/mg protein, N.S.). These findings were confirmed by immunocytochemistry, which demonstrated intense staining for GFAP and decreased staining for NfH(SM135) in CREAE compared to control animals. These findings indicate that axonal loss and gliosis can be estimated biochemically using the newly developed ELISA assays for NfH(SM135) and GFAP. These assays may facilitate the quantification of pathological features involved in neurodegeneration.

Animals↗

PubMed2003

Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Delta9-trans-tetrahydrocannabinol (Delta9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Delta9THC, at matched concentrations of Delta9THC, and also with a Delta9THC-free extract (Delta9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Delta9THC alone. The Delta9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Delta9THC, but in this model, the Delta9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Delta9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. antispasticity), Delta9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Delta9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Delta9THC content.

Animals↗

PubMed2001

Myelin/axonal pathology in interleukin-12 induced serial relapses of experimental allergic encephalomyelitis in the Lewis rat.

Lewis rats, on recovery from monophasic clinical experimental allergic encephalomyelitis (EAE), can be induced to develop repeated paralytic relapses with a graded reduction in clinical severity following intraperitoneal administration of IL-12. By the time of the third relapse, the number and size of inflammatory cuffs in the spinal cord were reduced with the makeup of the cellular infiltrate shifting to a significantly increased number of B cells. Serum levels of myelin basic protein (MBP)-specific IgG1 and IgG2b were found to rise over time while MBP and MBP peptide-positive macrophages and microglia became evident in perivascular cuffs and in spinal cord parenchyma, indicative of myelin phagocytosis. Axonal death was observed in semithin and EM sections of spinal cord in third relapse animals in association with iNOS and tPA immunostaining throughout gray and white matter. These neurotoxic or excitotoxic agents may contribute to axonal damage directly or indirectly by activated microglia and macrophages, leading to limited damage of the axonal-myelin unit.

Acute Disease↗

PubMed2000

Endocannabinoids control spasticity in a multiple sclerosis model.

Spasticity is a complicating sign in multiple sclerosis that also develops in a model of chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice. In areas associated with nerve damage, increased levels of the endocannabinoids, anandamide (arachidonoylethanolamide, AEA) and 2-arachidonoyl glycerol (2-AG), and of the AEA congener, palmitoylethanolamide (PEA), were detected here, whereas comparable levels of these compounds were found in normal and non-spastic CREAE mice. While exogenously administered endocannabinoids and PEA ameliorate spasticity, selective inhibitors of endocannabinoid re-uptake and hydrolysis-probably through the enhancement of endogenous levels of AEA, and, possibly, 2-arachidonoyl glycerol-significantly ameliorated spasticity to an extent comparable with that observed previously with potent cannabinoid receptor agonists. These studies provide definitive evidence for the tonic control of spasticity by the endocannabinoid system and open new horizons to therapy of multiple sclerosis, and other neuromuscular diseases, based on agents modulating endocannabinoid levels and action, which exhibit little psychotropic activity.

Amides↗

PubMed2000

Cannabinoids control spasticity and tremor in a multiple sclerosis model.

Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an autoimmune model of multiple sclerosis. Although both these diseases are typified by relapsing-remitting paralytic episodes, after CREAE induction by sensitization to myelin antigens Biozzi ABH mice also develop spasticity and tremor. These symptoms also occur during multiple sclerosis and are difficult to control. This has prompted some patients to find alternative medicines, and to perceive benefit from cannabis use. Although this benefit has been backed up by small clinical studies, mainly with non-quantifiable outcomes, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, delta9-tetrahydrocannabinol, methanandamide and JWH-133 (ref. 8) quantitatively ameliorated both tremor and spasticity in diseased mice. The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients' indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis, and provides a means of evaluating more selective cannabinoids in the future.

Animals↗

PubMed1997

Factors controlling T-cell migration across rat cerebral endothelium in vitro.

The migration of lymphocytes through primary cultures of rat brain microvascular endothelial cell monolayers was examined in vitro by time-lapse videomicroscopy. Antigen-specific T cell line migration was dependent on the duration of culture (post-antigen stimulation) with exogenous interleukin-2 (IL-2). Peak migration (approximately 50% of T-cells during the 4 h migration assay) occurred after 4 days of culture with IL-2 but did not coincide with maximal expression of LFA-1, VLA-4 or the IL-2 receptor. On unstimulated endothelia antibody blockade of LFA-1 or ICAM-1 inhibited T-cell line migration to 8.0% and 6.8% of control values, respectively, whereas blocking VLA-4 and VCAM-1 had no effect. On IL-beta activated endothelium blocking LFA-1 and ICAM-1 was less effective (24.9% and 27.3% of control values, respectively) and blockade of VLA-4 and VCAM-1 brought about a reduction to 63.0% and 68.3% of controls respectively. Inhibition of IL-2-dependent proliferation with an IL-2 receptor blocking antibody also significantly inhibited T-cell migration to 22.2% of controls. Peripheral lymph node (PLN) lymphocytes could also be induced to migrate through untreated cerebral endothelial cell monolayers by cross-linking CD3 which was also time and IL-2-dependent with maximal migration (22.7%) occurring after three days in the presence of exogenous IL-2. Blocking LFA-or ICAM-1 resulted in a significant reduction in migration across IL-1 beta-activated endothelial cells to 17.4% and 20.9% of control values respectively although blocking the VLA-4/VCAM-1 interaction had no significant effect. Activation of PLN lymphocytes with concanavalin A for up to 5 days did not induce migration but when left in contact with the endothelial monolayer for 24 h migration reached 31.0%. These studies indicate that T-cells require a combination of signals to trigger the migratory phenotype which is necessary to enable them to penetrate the blood-brain barrier.

Animals↗

PubMed1996

SV40 large T immortalised cell lines of the rat blood-brain and blood-retinal barriers retain their phenotypic and immunological characteristics.

In the central nervous system the blood-brain and blood-retinal barriers (BBB and BRB respectively) are instrumental in maintaining homeostasis of the neural parenchyma and controlling leucocyte traffic. These cellular barriers are formed primarily by the vascular endothelium of the brain and retina although in the latter the pigmented epithelial cells also form part of the barrier. From primary cultures of rat brain endothelium, retinal endothelium and retinal pigment epithelium (RPE) we have generated temperature sensitive SV40 large T immortalised cell lines. Clones of brain (GP8.3) and retinal (JG2.1) endothelia and RPE (LD7.4) have been derived from parent lines that express the large T antigen at the permissive temperature. The endothelial cell (EC) lines expressed P-glycoprotein, GLUT-1, the transferrin receptor, von Willebrand factor and the RECA-1 antigen and exhibited high affinity uptake of acetylated LDL and stained positive with the lectin Griffonia simplicifolia. The RPE cell line was positive for cytokeratins and for the rat RPE antigen RET-PE2. All the cell lines expressed major histocompatibility complex (MHC) class 1 and intercellular adhesion molecule (ICAM)-1 constitutively and could be induced to express MHC class II and vascular cell adhesion molecule (VCAM)-1 following cytokine activation. The EC also expressed platelet endothelial cell adhesion molecule (PECAM)-1. Monolayers of these cells could support the migration of antigen-specific T cell lines. The generation of immortalised cell lines derived from the rat BBB and BRB should prove to be useful tools for the study of these specialised cellular barriers.

Animals↗

PubMed1994

An assay for the analysis of lymphocyte migration across cerebral endothelium in vitro.

We describe a recently developed assay for the analysis of leukocyte migration across cerebral endothelium in vitro. The endothelium is grown as monolayers on Goretex or Cyclopore membranes coated with extracellular matrix proteins and supported on inserts. This system permits the recovery and phenotyping of cells which migrate down through the endothelium. Using labelled lymphocytes we were able to differentiate four populations of cells, with differing degrees of mobility in the migration assay. We have compared the results from this system with those from conventional adhesion assays. Binding of cells to the endothelium is rapid, but is confined to a particular subpopulation of the applied lymphocytes. We have followed cell migration over 24 h in the system using normal and cytokine-activated endothelium and have found that whereas adhesion depends both on the state of lymphocyte activation and on the condition of the endothelium, the level of migration of stimulated lymphocytes is largely independent of endothelial activation. Moreover, whereas CD8+ cells bind well to the endothelium, it is the CD4+ cells which migrate most effectively. Comparison of brain and epididymal fat endothelium showed similar migration levels over 2 h, but migration was greater across epididymal fat endothelium at 24 h.

Adipose Tissue↗

PubMed1994

Lymphocyte migration into the CNS modelled in vitro: roles of LFA-1, ICAM-1 and VLA-4.

We examined the changes in intercellular adhesion molecule-1 (ICAM-1) expression on brain endothelium in response to tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). ICAM-1 is normally present on these cells and is induced over 24 hr by both cytokines with a time-course which matches enhancement in lymphocyte adhesion. Anti-lymphocyte function-associated antigen-1 (anti-LFA-1) (CD11a), anti-very late antigen-4 (anti-VLA-4) (CD49d) and anti-CD18 block binding of mitogen-activated lymphocytes to brain endothelium and the effects of anti-LFA-1 and anti-VLA-4 are additive. Anti-ICAM-1 does not however block adhesion, nor does depletion of endothelial ICAM-1 reduce lymphocyte binding. Titration of the interacting cells indicated that the antibody blocking is due to interference in the endothelial/lymphocyte interaction. None of the antibodies affect the binding of non-activated lymphocytes, which is itself normally much lower than that of activated cells. The time at which lymphocyte adhesiveness is greatest for the endothelium corresponds with the time at which the lymphocytes express highest levels of LFA-1 and VLA-4. The data show a role for LFA-1 and VLA-4 in the early interaction of activated lymphocytes with brain endothelium. Kinetic studies indicate that the ligand for VLA-4 is VCAM-1. The ligand for LFA-1 could not be determined with certainty, but if it is ICAM-1, the levels of ICAM-1 on brain endothelium are not critical.

Animals↗

PubMed1992

Lymphocyte migration into the CNS modelled in vitro.

We report on a series of experiments which examines the factors controlling lymphocyte adhesion to brain endothelium in vitro and the factors which control cell migration across the endothelium, using a new migration assay. Although lymphocyte adhesion preceded migration across the brain endothelium, the two processes are not identical. We noted that activated CD4+ T cells were particularly good at migrating across endothelia. CD8+ T cells and B cells did not migrate but adhered well to endothelia. Moreover, the endothelium maintained high levels of cell traffic without being disrupted and without exhausting the molecular systems which allowed migration. From the viewpoint of migration of dividing cells, the state of lymphocyte activation appeared to be the most important controlling factor--these cells migrated equally well across endothelium activated with cytokines or untreated endothelium. The kinetics of adhesion suggested that the LFA-1/ICAM-1 and VLA-4/VCAM combinations of adhesion molecules were important in controlling migration. With antibody blocking studies, the role of the LFA-1/ICAM-1 system was equivocal. While anti-LFA-1 blocked lymphocyte adhesion, anti-ICAM-1 did not, suggesting that the level of ICAM-1 was not critical.

Animals↗

PubMed1991

Control of lymphocyte migration into brain: selective interactions of lymphocyte subpopulations with brain endothelium.

We have determined whether particular lymphocyte populations bind preferentially to cerebral endothelium, using adhesion assays and a new method for in situ staining of adherent lymphocytes. B cells bind more strongly than T cells, an effect enhanced by lymphocyte activation or endothelial cell stimulation with interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha). This is not equated with levels of CD18 expression on the lymphocytes. CD8+ T cells bound more efficiently than CD4+ cells under all conditions. To determine whether there was a population of cells which selectively homes to the brain, we compared adhesion of cervical lymph nodes cells to brain endothelium, with adhesion of lymphocytes from other nodes. In 50% of the experiments there was significantly enhanced binding of activated cervical lymph cells to cerebral endothelium but not to control (aortic) endothelium. This effect was seen using both normal and IFN-gamma-activated endothelium. The explanation for this finding is that cervical lymph nodes frequently, but not invariably, contain higher proportions of CD8+ cells and B cells than other lymph nodes. These data imply that selective adhesion of lymphocytes to brain endothelium is related to the subpopulations involved and this may be reflected in the cell types seen in immunological lesions of the brain, and in the relative proportions of the subpopulations seen in cervical lymph nodes.

Animals↗

PubMed1990

Comparison of the immunological properties of rat cerebral and aortic endothelium.

The immunological properties of cerebral microvascular endothelium were directly compared with those of an extra-cerebral endothelium in vitro. Lymphocyte adhesion to cerebral endothelium is normally low, but is sensitive to induction by interferon-gamma (IFN gamma) and tumour necrosis factor-alpha (TNF alpha). Conversely adhesion to aortic endothelium is normally much higher but it is only marginally sensitive to induction by cytokines. Adhesion to both cell types is Ca2+ and Mg2+ dependent. Mitogen-activated lymphocytes bind more strongly to both endothelia, but adhesion to aortic endothelium is not enhanced further by activation of the endothelium. The observed low binding of lymphocytes to brain endothelium and its rapid induction by cytokines suggest a mechanism to explain why lymphocyte accumulation in brain is normally very low but rapidly increases during immune responses. Both cell types express similar levels of class I major histocompatibility complex (MHC) molecules, and this is enhanced by IFN gamma with similar responsiveness to different levels of IFN gamma. MHC class II molecules are absent from these cells but may be induced: although both endothelia respond to similar levels of cytokines, the surface density induced on brain endothelium is approximately 2- to 3-fold higher at all levels of IFN gamma.

Animals↗

PubMed1989

Induction of Ia molecules on brain endothelium is related to susceptibility to experimental allergic encephalomyelitis.

We have examined the responses of brain endothelium from different rat strains to interferon-gamma (IFN-gamma) which induces expression of MHC class II molecules. There is a marked difference between the strains in the sensitivity of their endothelium to MHC induction. LEW and DA rats, which are susceptible to experimental allergic encephalomyelitis (EAE) can be induced to express higher levels of class II molecules than EAE-resistant strains. In both the EAE-susceptible and -resistant strains, RT-1B locus-encoded molecules occur at higher surface densities than RT-1D locus molecules. These findings support the theory that genes controlling the induction of MHC expression affect disease susceptibility.

Animals↗

PubMed1989

Antigen presentation in brain: brain endothelial cells are poor stimulators of T-cell proliferation.

The capacity of rat brain capillary endothelium to present antigen to primed peripheral lymph node cells or to ovalbumin-specific T-cell lines was examined in vitro. Brain endothelium can present antigen, but it is generally ineffective at stimulating T-cell division. Division is only seen when indomethacin is included in the cultures to suppress eicosanoid production. Even under these conditions an endothelial monolayer is only 1/40 as effective as a thymocyte monolayer in stimulating division. The failure to act as an effective antigen presenting tissue is not due to lack of IL-1 production, nor is it related to the extended time required to induce MHC class II molecules on these cells. In the presence of high levels of antigen-specific T cells, the endothelium appears to be subject to cytotoxic damage, so that T-cell stimulation is lowest with higher numbers of T cells--the opposite of that seen with conventional antigen-presenting cells. These findings support the view that brain endothelial cells are not important in stimulating T-cell division during the development of immune reactions in brain, although these cells may be recognizable by class II-restricted cytotoxic cells.

Animals↗

PubMed1988

Synergy between interferons and monokines in MHC induction on brain endothelium.

Rat brain endothelial cells were cultured as confluent monolayers and stimulated with combinations of interferon-beta (IFN beta), interferon-gamma (IFN gamma), tumour necrosis factor (TNF) and interleukin 1 (IL-1). After 4 days of stimulation the cell surface expression of class I and class II MHC molecules was quantitated by enzyme immunoassay. TNF by itself enhances class I expression and it synergises with IFN gamma in enhancing class I expression and inducing class II. IL-1 does not affect class I expression, nor does it synergise with IFN gamma in this respect. High doses of IL-1 slightly reduce IFN gamma mediated class II induction, but have no synergistic effect at lower doses. IFN beta stimulates class I weakly and induced class II in one experiment but the effects seen when IFN gamma and IFN beta were used together were additive, not synergistic. IFN gamma is the most potent modulator of MHC expression on these cells, although TNF acts as a strong co-stimulator, while IL-1 and IFN beta have only minor effects.

Animals↗