Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study explores nasal administration of myelin basic protein (MBP) as a potential means of inducing tolerance to relapsing experimental autoimmune encephalomyelitis (PR-EAE), an experimental multiple sclerosis (MS) model that was induced in DA rats by immunization with rat spinal cord homogenate and incomplete Freund's adjuvant. DA rats received a total dosage of 0, 6, 60, 600 micrograms/rat of bovine MBP on ten consecutive days prior to immunization. EAE with typical course was observed in control rats receiving only PBS nasally, and in rats receiving 6 micrograms/rat of MBP. Rats receiving 60 micrograms/rat of MBP developed acute EAE but no relapse during 60 days of observation post immunization (p.i.). Only one of eight rats receiving 600 micrograms/rat of MBP developed slight, transient EAE. This protection was confirmed at the histology level and was associated with decreased levels of MBP-reactive IFN-gamma secreting Th1-like spleen cells on day 13 and 60 p.i. Rats receiving 60 and 600 micrograms/rat of MBP showed decreased serum anti-MBP IgG2b antibody levels on day 60 p.i., and rats receiving 600 micrograms/rat of MBP had marginally increased anti-MBP IgG1 antibody levels in serum compared to control EAE rats. Cytokine mRNA profiles in central nervous system (CNS) and spleen mononuclear cells were evaluated. Dose-dependent reduction of TNF-alpha mRNA expression were observed both in CNS and in splenocytes. Increased IL-4 and TGF-beta mRNA expression were observed in CNS of low (6 micrograms/rat) and median (60 micrograms/rat) dose of MBP tolerized rats and in splenocytes of rats tolerized with 600 micrograms/rat of MBP. We conclude that nasal administration of MBP in DA rat prevents EAE induced by immunization with whole rat spinal cord homogenate that, besides MBP, contains multiple antigenic myelin proteins. A mechanism involving MBP-reactive regulatory cells expressing IL-4 and TGF-beta mRNA acts as part in the induction of this tolerance.
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PMID:Nasal administration of myelin basic protein prevents relapsing experimental autoimmune encephalomyelitis in DA rats by activating regulatory cells expressing IL-4 and TGF-beta mRNA. 941 60

We have studied the effects of either exogenously-administered interferon (IFN-)gamma or of a nonimmunogenic mouse IFN-gamma receptor-Immunoglobulin (IFN-gamma R-Ig) fusion protein on the development of Concanavalin (Con)A-induced hepatitis in NMRI mice. PBS-treated control mice injected with 20 mg/kg ConA developed classical serological and histological signs of hepatitis with elevation of transaminases in the blood and infiltration of the liver by mononuclear cells and neutrophils. Treating the mice with rat IFN-gamma 24 h prior to and 1 h after ConA-challenge markedly exacerbated these signs of hepatitis in a dose-dependent fashion. Moreover, mice injected with lower, non hepatitogenic, doses of ConA (10, 5 mg/kg) became fully susceptible to develop hepatitis upon similar treatment with IFN-gamma. Concordantly, ConA-induced hepatitis was abrogated by either IFN-gamma R-Ig fusion protein or anti-IFN-gamma mAb. These data provide further evidence for the central pathogenetic role of endogenous IFN-gamma in ConA-induced hepatitis and demonstrate the feasibility to prevent disease development by means of a non immunogenic IFN-gamma R-Ig fusion protein.
Cytokine 2000 Apr
PMID:Essential pathogenetic role for interferon (IFN-)gamma in concanavalin A-induced T cell-dependent hepatitis: exacerbation by exogenous IFN-gamma and prevention by IFN-gamma receptor-immunoglobulin fusion protein. 1080 11

IL-18 expression has recently been detected in rheumatoid arthritis (RA) synovial membrane. We investigated the mechanisms by which IL-18-induced collagen-induced arthritis in DBA/1 mice primed intradermally with type II bovine collagen in IFA and boosted i.p. 21 days later with CII in saline. Mice were injected i.p. with rIL-12, rIL-18, or both (100 ng) during days -1 to 4 and again on days 20-24. Control mice received PBS. Mice treated with IL-12 or IL-18 alone developed significantly higher incidence and more severe disease compared with controls. These were elevated further by combination treatment with IL-12 and IL-18. The cytokine treatments led to markedly enhanced synovial hyperplasia, cellular infiltration, and cartilage erosion compared with controls. Cytokine-treated mice produced significantly more IFN-gamma, TNF-alpha, and IL-6 than the controls. Interestingly, IL-18-treated mice produced more TNF-alpha and IL-6, but less IFN-gamma, compared with mice treated with IL-12. Furthermore, splenic macrophages from DBA/1 mice cultured in vitro with IL-18, but not IL-12, produced substantial amounts of TNF-alpha. Mice treated with IL-18 or IL-18 plus IL-12 produced markedly more IgG1 and IgG2a anti-collagen Ab compared with controls, whereas IL-12 treatment only led to an enhanced IgG2a response. Together these results demonstrate that IL-18 can promote collagen-induced inflammatory arthritis through mechanisms that may be distinct from those induced by IL-12.
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PMID:Combined effects of IL-12 and IL-18 on the induction of collagen-induced arthritis. 1084 7

To examine the direct effects of IL-4 on peripheral nervous system (PNS) we injected recombinant rat IL-4 (rrIL-4) into the sciatic nerve of normal adult Lewis rats. Histopathological and immunohistochemical observations revealed that 1 day after injection, a large number of macrophages and MHC class II-positive cells appeared within both the perineurium and endoneurium. Only few CD4(+)and CD8(+)T cells existed in the endoneurium. From day 4 to day 7, we observed a gradual decline of inflammation, but the number of infiltrates in rrIL-4 injected nerves was significantly higher compared with sterile PBS-injected control group. On the contrary, demyelination affected significantly fewer nerve fibres in the rrIL-4-injected nerves compared with control group on day 7. Intraneural injection of rrIL-4 results in high grade inflammation and mild demyelination in the PNS.
Cytokine 2000 Jun
PMID:High inflammation and mild demyelination in the peripheral nervous system induced by an intraneural injection of RR interleukin-4. 1084 69

Safety and bioavailability of pulmonary delivered interferon-beta 1a (IFN-beta1a, AVONEX, Biogen, Inc., Cambridge, MA) was evaluated in the nonhuman primate. Pulmonary bioavailability following intratracheal (i.t.) instillation of 50 microg/kg IFN-beta1a to rhesus macaques was approximately 10%. To evaluate pulmonary safety, IFN-beta1a was administered intrabronchially to rhesus and cynomolgus macaques at a dose of 60 microg/dose one, three, or seven times per week for 4 weeks. At scheduled termination, lungs were evaluated for gross and histomorphologic changes. IFN-beta1a or vehicle (human serum albumin [HSA] in phosphate-buffered saline [PBS]) treatment resulted in minimal to mild subchronic alveolitis, located primarily near the instillation sites. These responses were considered nonspecific and consistent with either instillation of a foreign protein or minor injury associated with the instillation procedure. In one rhesus macaque treated every day for 4 weeks, IFN-beta1a induced mild to moderate eosinophilic alveolitis, considered possibly an isolated type I hypersensitivity response to HSA or IFN-beta1a. Partial resolution of pulmonary lesions was seen in all recovery animals killed 2 weeks after cessation of treatment. In conclusion, this study shows that pulmonary administration of human IFN-beta1a is safe and that the pulmonary route of administration is a possible alternate route for the systemic delivery of IFN-beta1a.
J Interferon Cytokine Res 2002 Jun
PMID:Safety and systemic absorption of pulmonary delivered human IFN-beta1a in the nonhuman primate: comparison with subcutaneous dosing. 1216 83

The aim of this study was to determine therapeutic effects of complete Freund's adjuvant (CFA) on the progression and relapsing of pristine-induced arthritis (PIA) and investigate the mechanism involved. Chronic relapsing arthritis was induced by pristine in LEW rats. After onset of arthritis, rats were intradermally injected CFA and rats in control group were injected the same volume of PBS. Arthritis was monitored visually, and joint pathology was examined histologically. Cytokine mRNA expression in inguinal lymph nodes was assessed by RT-PCR. The levels of nitric oxide (NO) in serum were measured by colorimetric assay. The results showed that CFA significantly suppressed the progression and relapsing of PIA. Relapsing rate of PIA in CFA-treated group was 12.5% and it was 85.7% in PBS-control group (P < 0.005). CFA markedly inhibited the infiltration of inflammatory cells and cartilage damage in the joints of CFA-treated rats and promoted the increases of IFN-y mRNA and NO levels. The present study provided an implication that adjuvant therapy may be a new strategy for the treatments of rheumatoid arthritis (RA) and other chronic inflammatory diseases.
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PMID:Complete Freund's adjuvant promotes the increases of IFN-gamma and nitric oxide in suppressing chronic arthritis induced by pristane. 1452 77

Cytokine growth factor treatment of chronic wounds has met with mixed results. The chronic wound presents a hostile environment to peptides such as growth factors. Cytokine growth factors have not been studied extensively in acute wounds. However, incisional hernias are a major example of acute wound failure that has not been solved by various mechanical approaches. A biological approach to acute wound failure by use of cytokine growth factors may offer a new strategy. A rodent incisional hernia model was used. Seventy-six rats underwent 3-cm midline celiotomies and were closed with fine, fast-absorbing sutures to induce intentional acute wound failure. Group 1 received no other treatment. The midline fascia in Groups 2-10 was infiltrated with 100 microl of vehicle alone or vehicle containing various test cytokine growth factors. Necropsy was performed on postoperative day 28 and the wounds were examined for herniation. Incisional hernias developed in 83 percent (13/16) of untreated incisional and 88 percent (7/8) and 83 percent (5/6) of the two vehicle-treated incisions (PBS and carboxymethylcellulose). Hernia incidences were decreased by priming of the fascial incision with transforming growth factor-beta(2) (12%, 1/8), basic fibroblast growth factor (25%, 2/8) and interleukin-1 beta (50%, 3/6) (p < 0.05). Aqueous platelet-derived growth factor, becaplermin, insulin-like growth factor, and granulocyte macrophage-colony stimulating factor did not significantly decrease the incidence of acute wound failure (p > 0.05). A biological approach to acute wound failure as measured by incisional hernia formation can be useful in reducing the incidence of this complication. Transforming growth factor-beta(2), basic fibroblast growth factor, and interleukin 1 beta all eliminated or significantly reduced the development of incisional hernias in the rat model.
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PMID:Effect of cytokine growth factors on the prevention of acute wound failure. 1497 63

Recent clinical trials have shown that the new generation of acellular pertussis vaccines (Pa) can confer protection against whooping cough with negligible adverse reactions. We have compared the effects of pertussis whole cell and acellular vaccines on pulmonary immune responses after aerosol challenge in a murine model of infection. Mice were vaccinated with PBS, Pw or Pa and challenged with Bordetella pertussis by the aerosol route. Cytokine gene expression was analysed from lung tissue and cells; lung lymphocytes were re-stimulated in vitro and cytokines produced measured. The results obtained are consistent with the proposal that a strong Th-1 response is associated with bacterial clearance in both the non-vaccinated and Pw vaccinated mice. The acellular vaccine treated mice cleared the bacterial challenge (with an intermediate efficacy) in the presence of low levels of any of the cytokines assessed. This suggests that Pa protects via a Th-2 independent mechanism.
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PMID:The effect of pertussis whole cell and acellular vaccines on pulmonary immunology in an aerosol challenge model. 1505 14

Cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 is known to exert a neurotrophic action in the central nervous system, although the role of this signaling in cerebral ischemia remains unknown. We examined the effect of intracerebral injection of LIF after focal cerebral ischemia in rats. The animals underwent a sham operation (sham group) or middle cerebral artery occlusion (MCAO) followed by direct injection of either vehicle (phosphate-buffered saline, the PBS group) or recombinant LIF (10 ng in the low-LIF group and 100 ng in the high-LIF group) into the cerebral cortex adjacent to the inner boundary zone of the infarct area, and neurologic and histologic evaluations were conducted 24 h later. Expression of LIFR, gp130, and phosphorylated Stat3, Akt, and ERK1/2 was investigated by Western blot analysis and immunohistochemistry. The neurologic deficits and ischemic damage were significantly less severe in the high-LIF group than in the PBS group and the low-LIF group. Leukemia inhibitory factor receptor and gp130 were expressed in neurons, and the ischemic damage of these proteins was rescued in the high-LIF group. Early induction of phosphorylated Stat3 was significantly detected on the ischemic side in the high-LIF group after LIF injection. Exogenous LIF attenuates ischemic brain injury by activating cytokine signaling through LIFR/gp130.
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PMID:Activation of cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 attenuates ischemic brain injury in rats. 1571 58

To gain insight into aberrant cytokine regulation in cystic fibrosis (CF), we compared the phenotypic manifestations of allergen challenge in gut-corrected CFTR-deficient mice with background-matched C57Bl6 (B6) mice. Aspergillus fumigatus (Af) antigen was used to mimic allergic bronchopulmonary aspergillosis, a peculiar hyper-IgE syndrome with a high prevalence in CF patients. CFTR-/-, C57BL/6 and FVB/NJ mice were sensitized with Af antigen by serial intraperitoneal injections. Control mice were mock sensitized with PBS. Challenges were performed by inhalation of Af antigen aerosol. After Af antigen challenge, histologic analysis showed goblet cell hyperplasia and lymphocytic infiltration in both strains. However, total serum IgE levels were markedly elevated in CF mice. Sensitized CF mice showed a five-fold greater IgE response to sensitization as compared with B6- and FVB-sensitized controls. Additional littermate controls to fully normalize for B6-FVB admixture in the strain background confirmed the role of CFTR mutation in the hyper-IgE syndrome. Cytokine mRNA levels of IL-5 and GM-CSF in the bronchoalveolar lavage (BAL) fluid, and BAL cell differentials indicated that CFTR mutation caused a shift from an IL-5-predominant to an IL-4-predominant cytokine profile. This system models a very specific type of airway inflammation in CF and could provide insights into pathogenesis and treatment of the disease.
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PMID:Enhanced IgE allergic response to Aspergillus fumigatus in CFTR-/- mice. 1642 81


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