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1.
Concanavalin A-induced hepatitis in mice is prevented by interleukin (IL)-10 and exacerbated by endogenous IL-10 deficiency 总被引:3,自引:0,他引:3
Di Marco R Xiang M Zaccone P Leonardi C Franco S Meroni P Nicoletti F 《Autoimmunity》1999,31(2):75-83
One single intra-venous (i.v.) injection of Concanavalin A (Con A) into mice provokes a cell-mediated immunoinflammatory hepatitis. We have presently evaluated the immunopharmacological effects of exogenous interleukin (IL)-10 and the role of endogenous IL-10 in this model by using exogenous IL-10, anti-IL-10 monoclonal antibody (mAb) and mice with disrupted IL-10 gene (IL-10 KO mice). Whilst exogenous IL-10 administered in a prophylactic (1 h prior to Con A) and even "early" therapeutic fashion (30 min after Con A) reduced the elevation of transaminase activities in plasma in a dose-dependent manner, observed in control mice, these biochemical markers of liver injury were significantly increased both in IL-10 KO mice as well as in those receiving anti-IL-10 mAb. Interestingly, doses of Con A lower than 20 mg/kg that were only capable of inducing slight serological signs of hepatitis in mice, exerted marked hepatitic effects when administered to either anti-IL-10 mAb-treated mice or to IL-10 KO mice. The disease modulating effects of exogenous IL-10 and either genetical or pharmacologically-induced IL-10 deficiency were associated with profound and opposite modifications of the Con A-induced increase in the circulating levels of IFN-gamma and TNF-alpha. Relative to control animals, the blood levels of these cytokines were diminished in IL-10-treated mice and augmented in both IL-10 KO mice and anti-IL-10 mAb-treated mice. These results prove the physiological antiinflammatory role of endogenous IL-10 in Con A induced hepatitis and the beneficial effects of IL-10 treatment to prevent this condition. 相似文献
2.
Ferdinando Nicoletti Giuseppe Mancuso Vitaliano Cusumano Roberto Di Marco Paola Zaccone Klaus Bendtzen Giuseppe Teti 《European journal of immunology》1997,27(6):1580-1583
Interleukin(IL)-13, a cytokine produced by T helper 2 (Th2) cells, is a powerful inhibitor of macrophage functions, including surface expression of CD14 and production of IL-1 and tumor necrosis factor (TNF)-α. We tested the effects of recombinant mouse(m)IL-13 in a neonatal mouse model of endotoxin shock; this is a macrophage-dependent condition, which is a model of neonatal sepsis in humans. mIL-13 (0.5 μg/mouse) dramatically reduced the lethal effects of lipopolysaccharide (LPS) if administered either 24 or 4 h prior to or concomitantly with LPS challenge. This action might be mediated by multiple modulatory activities of IL-13 on LPS-induced cytokine secretion since, relative to control animals, the mice treated with mIL-13 had eight times lower peak blood levels of TNF. The IL-1β levels were also decreased, whereas increased levels of IL-6 and IL-10 were observed at several time points after LPS challenge. 相似文献
3.
Infection with Mycobacterium avium induces production of interleukin-10 (IL-10), and administration of anti-IL-10 antibody is associated with enhanced resistance to infection in mice. 总被引:17,自引:8,他引:9
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Organisms of the Mycobacterium avium complex are associated with disseminated infection in patients with AIDS. The mechanisms that account for the survival of the intracellular bacteria are unknown. We document here that infection of C57BL/6 black mice with M. avium 101 triggered interleukin-10 (IL-10) production. The synthesis of IL-10 peaked after 2 weeks of infection and remained elevated throughout the period of infection. Treatment of M. avium-infected peritoneal macrophages with recombinant IL-10 suppressed the stimulatory effect of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. To confirm the possible role of IL-10 in the infection in vivo, mice were infected with M. avium 101 and simultaneously received treatment with neutralizing anti-IL-10 antibody. After 4 weeks the animals were harvested and the numbers of viable bacteria were quantitated in the liver, spleen, and blood. The liver and spleen of animals receiving anti-IL-10 antibody had 2 to 3 log units fewer bacteria than did those of control animals. These results suggest a role for IL-10 in the pathogenesis of M. avium infection. 相似文献
4.
Erik Martens Chris Dillen Willy Put Hubertine Heremans Jo van Damme Alfons Billiau 《European journal of immunology》1993,23(8):2026-2029
Mice pretreated with monoclonal anti-interleukin-6 (IL-6) antibody and then challenged with lipopolysaccharide (LPS), paradoxically develop higher levels of circulating biological IL-6 activity, as measured by the hybridoma growth promotion assay, than mice similarly challenged but not pretreated with antibody. Here we provide evidence that this increased biological activity was entirely accounted for by the presence of increased amounts of IL-6 protein, which could be isolated by immunoaffinity chromatography and subsequently visualized after gel electrophoresis. Chromatography on a protein G matrix and a sandwich ELISA allowed to demonstrate that all IL-6 present in the serum was in the form of antigen-antibody complexes. Serum samples of antibody-treated animals which contained the highest biological activity typically contained near equimolar concentrations of IL-6 and antibody. In vitro neutralization tests with pure antibody and IL-6 demonstrated that, with both antibodies tested, more than 1000-fold molar excess of antibody is needed for neutralization in the hybridoma growth assay. It is concluded that increased biological activity in serum of the anti-IL-6 antibody-treated mice is due to sequestration of the endogenous IL-6 in the form of antigen-antibody complexes which, due to the lack of sufficient antibody excess, produce nearly full activity in the hybridoma growth assay. 相似文献
5.
Regulation of parasite antigen-driven immune responses by interleukin-10 (IL-10) and IL-12 in lymphatic filariasis. 总被引:8,自引:1,他引:8
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S Mahanty M Ravichandran U Raman K Jayaraman V Kumaraswami T B Nutman 《Infection and immunity》1997,65(5):1742-1747
We investigated the mechanisms by which interleukin-10 (IL-10) regulates antigen-specific hyporesponsiveness in asymptomatic microfilaremic (MF) individuals. Peripheral blood mononuclear cells from MF individuals (n = 11) were stimulated in vitro with Brugia malayi antigen (BMA) or mycobacterial purified protein derivative (PPD) in the presence of neutralizing anti-IL-10 or isotype control monoclonal antibodies. As expected, BMA stimulated little or no gamma interferon (IFN-gamma) secretion in MF individuals, whereas PPD stimulated IFN-gamma in all but one. Neutralization of endogenous BMA-driven IL-10 secretion led to augmentation of IFN-gamma in seven of nine MF individuals (1.5- to 10-fold) and did so in a BMA-specific manner (PPD-driven IFN-gamma was augmented in only two of eight MF individuals and only 1.5- to 2-fold), indicating that IL-10 downregulates type 1 responses in these individuals. Type 2 responses (IL-5 secretion) were unaffected by the IL-10 blockade. To assess whether IL-12 could reverse the type 1 downregulation observed, the effect of recombinant human IL-12 (rhIL-12) on BMA-driven IL-5 and IFN-gamma production was also evaluated. rhIL-12 augmented both BMA- and PPD-driven IFN-gamma production 5- to 10-fold in six of nine MF individuals. These data demonstrate that IL-10 downregulates BMA-driven type 1 responses and that IL-12 can overcome downregulation of Th1 responses associated with MF but does so in a non-antigen-specific manner. 相似文献
6.
Gallagher G Dickensheets H Eskdale J Izotova LS Mirochnitchenko OV Peat JD Vazquez N Pestka S Donnelly RP Kotenko SV 《Genes and immunity》2000,1(7):442-450
Interleukin-10 (IL-10) is a pleiotropic cytokine with important immunoregulatory functions whose actions influence activities of many of the cell-types in the immune system. We report here identification and cloning of a gene and corresponding cDNAs encoding a novel homologue of IL-10, designated IL-19. IL-19 shares 21% amino acid identity with IL-10. The exon/intron structure of IL-19 is similar to that of the human IL-10 gene, comprising five exons and four introns within the coding region of the IL-19 cDNA. There are at least two distinct IL-19 mRNA species that differ in their 5'-sequences, suggesting the existence of an intron in the 5'-sequences of coding portion of the IL-19 gene. The longer 5'-sequence contains an alternative initiating ATG codon that is in-frame with the rest of the coding sequence. The expression of IL-19 mRNA can be induced in monocytes by LPS-treatment. The appearance of IL-19 mRNA in LPS-stimulated monocytes was slightly delayed compared to expression of IL-10 mRNA: significant levels of IL-10 mRNA were detectable at 2 h post-stimulation, whereas IL-19 mRNA was not detectable until 4 h. Treatment of monocytes with IL-4 or IL-13 did not induce de novo expression of IL-19, but these cytokines did potentiate IL-19 gene expression in LPS-stimulated monocytes. In addition, GM-CSF was capable of directly inducing IL-19 gene expression in monocytes. IL-19 does not bind or signal through the canonical IL-10 receptor complex, suggesting existence of an IL-19 specific receptor complex, the identity of which remains to be discovered. 相似文献
7.
8.
Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26 总被引:5,自引:0,他引:5
Oral HB Kotenko SV Yilmaz M Mani O Zumkehr J Blaser K Akdis CA Akdis M 《European journal of immunology》2006,36(2):380-388
The family of IL-10-related cytokines includes several human members, IL-19, IL-20, IL-22, IL-24 and IL-26, and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival ad expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA(+) T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles. After three to four cycles of stimulation, IL-10 and CMV-IL-10 led to increased IFN-gamma and IL-10 but decreased IL-4 and IL-13. Interestingly, long-term exposure of T cells to IL-19, IL-20 and IL-22 down-regulated IFN-gamma but up-regulated IL-4 and IL-13 in T cells and supported the polarization of naive T cells to Th2-like cells. In contrast, neutralization of endogenous IL-22 activity by IL-22-binding protein decreased IL-4, IL-13 and IFN-gamma synthesis. The antigen-specific suppressor activity of IL-10 and CMV-IL-10 was not observed for any of the other IL-10-family cytokines. These data demonstrate that IL-19, IL-20 and IL-22 may participate in T cell-mediated diseases by distinct regulation of T cell cytokine profiles. 相似文献
9.
Dysregulated production of interleukin-10 (IL-10) and IL-12 by peripheral blood lymphocytes from human immunodeficiency virus-infected individuals is associated with altered proliferative responses to recall antigens. 总被引:1,自引:0,他引:1
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M P Daftarian F Diaz-Mitoma W D Creery W Cameron A Kumar 《Clinical and Vaccine Immunology : CVI》1995,2(6):712-718
The loss of immune function following infection with human immunodeficiency virus (HIV) may result from altered production of immunoregulatory cytokines such as interleukin-10 (IL-10) and IL-12. In this study, we analyzed IL-10 and IL-12 production by mitogen-stimulated peripheral blood mononuclear cells (PBMC) from HIV+ individuals and correlated their levels with proliferative responses to the recall antigens HIV p25 and influenza virus. We report two distinct groups of HIV+ patients. One group produced small amounts of IL-10, had PBMC that proliferated in response to recall antigens, and demonstrated enhanced recall antigen-induced proliferation upon addition of anti-IL-10 antibodies and/or IL-12. Conversely, the second group produced high levels of IL-10, had PBMC that failed to proliferate to recall antigens, and did not demonstrate enhanced proliferation upon addition of anti-IL-10 antibodies and/or IL-12. Mitogen-stimulated PBMC from both groups produced significantly lower levels of IL-12 than did those from HIV- controls. Analysis of the source of the IL-10-producing cell subset in PBMC demonstrated that in HIV+ individuals, IL-10 is produced by monocytes, while in HIV- controls, it is produced by both T cells and monocytes. Taken together, our results suggest that monocytes from HIV+ individuals secrete decreased amounts of IL-12, a Th1-type cytokine, which may lead to the development of Th2-type responses characterized by high IL-10 secretion and immune dysfunction. 相似文献
10.
Etling MR Davies S Campbell M Redline RW Fu P Levine AD 《Journal of leukocyte biology》2007,82(2):311-319
Elevated mucosal IL-12/23p40 and IFN-gamma accompany early inflammation in IL-10-deficient (IL-10(-/-)) mice and then later decline while inflammation persists. This report addresses whether this cytokine profile reflects disease progression or inherent, age-related changes in mucosal immunity. IL-10(-/-) and wild-type (WT) mice were maintained in an ultrabarrier facility or transferred to conventional housing at 3, 12, or 30 weeks of age. Weight, stool changes, and histologic features were followed. Lamina propria mononuclear cells were cultured for cytokine analysis by ELISA. Ultrabarrier-housed IL-10(-/-) mice are statistically indistinguishable from WT mice by weight, disease activity index, and histologic inflammation. IL-10(-/-) mice but not WT, transferred at 3 weeks, develop colitis gradually, reaching a significant, sustained maximum by 15 weeks of age. Transfer at 12 weeks induces rapid disease onset in both strains, maximal at 15 weeks of age. Inflammation persists in IL-10(-/-), and WT recover. IL-10(-/-) and WT mice transferred at 30 weeks demonstrate transient diarrhea and weight loss but no chronic inflammation. Probiotics delay symptom onset only in the 12-week-old group. IFN-gamma production from ultrabarrier-housed IL-10(-/-) mice is elevated at 12 weeks of age, and older animals have decreased IFN-gamma and increased IL-4. IL-10 is important for suppressing inflammation after transfer at 3 weeks of age and limiting inflammation after transfer at 12 weeks but has little influence at 30 weeks of age. Colitis onset, progression, and response to probiotic therapy vary with immune system age, suggesting that a distinct, Th1-driven, age-dependent cytokine profile may contribute to increased colitis susceptibility in otherwise healthy mice. 相似文献
11.
Human peripheral blood contains antigen-presenting cells (APC), including dendritic cells (DC) and monocytes, that may encounter microbes that have translocated from the intestine to the periphery in disease states like HIV-1 infection and inflammatory bowel disease. We investigated the response of DC and monocytes in peripheral blood mononuclear cells (PBMC) to a panel of representative commensal enteric bacteria, including Escherichia coli, Enterococcus sp., and Bacteroides fragilis. All three bacteria induced significant upregulation of the maturation and activation markers CD40 and CD83 on myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC). However, only mDC produced cytokines, including interleukin-10 (IL-10), IL-12p40/70, and tumor necrosis factor alpha (TNF-α), in response to bacterial stimulation. Cytokine profiles in whole PBMC differed depending on the stimulating bacterial species: B. fragilis induced production of IL-23, IL-12p70, and IL-10, whereas E. coli and Enterococcus induced an IL-10-predominant response. mDC and monocyte depletion experiments indicated that these cell types differentially produced IL-10 and IL-23 in response to E. coli and B. fragilis. Bacteroides thetaiotaomicron did not induce levels of IL-23 similar to those of B. fragilis, suggesting that B. fragilis may have unique proinflammatory properties among Bacteroides species. The addition of recombinant human IL-10 to PBMC cultures stimulated with commensal bacteria abrogated the IL-23 response, whereas blocking IL-10 significantly enhanced IL-23 production, suggesting that IL-10 controls the levels of IL-23 produced. These results indicate that blood mDC and monocytes respond differentially to innate stimulation with whole commensal bacteria and that IL-10 may play a role in controlling the proinflammatory response to translocated microbes. 相似文献
12.
Role of interleukin-18 (IL-18) in mycobacterial infection in IL-18-gene-disrupted mice 总被引:13,自引:0,他引:13
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Immunity to mycobacterial infection is closely linked to the emergence of T cells that secrete cytokines, gamma interferon (IFN-gamma), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha), resulting in macrophage activation and recruitment of circulating monocytes to initiate chronic granuloma formation. The cytokine that mediates macrophage activation is IFN-gamma, and, like IL-12, IL-18 was shown to activate Th1 cells and induce IFN-gamma production by these cells. In order to investigate the role of IL-18 in mycobacterial infection, IL-18-deficient mice were infected with Mycobacterium tuberculosis and Mycobacterium bovis BCG Pasteur, and their capacities to control bacterial growth, granuloma formation, cytokine secretion, and NO production were examined. These mice developed marked granulomatous, but not necrotic, lesions in their lungs and spleens. Compared with the levels in wild-type mice, the splenic IFN-gamma levels were low but the IL-12 levels were normal in IL-18-deficient mice. The reduced IFN-gamma production was not secondary to reduced induction of IL-12 production. The levels of NO production by peritoneal macrophages of IL-18-deficient and wild-type mice did not differ significantly. Granulomatous lesion development by IL-18-deficient mice was inhibited significantly by treatment with exogenous recombinant IL-18. Therefore, IL-18 is important for the generation of protective immunity to mycobacteria, and its main function is the induction of IFN-gamma expression. 相似文献
13.
Arias J Melean E Valero N Pons H Chacín-Bonilla L Larreal Y Bonilla E 《Investigación clínica》2003,44(1):41-50
The influence of Melatonin (MLT) on the modulation of the immune system has been described. In previous studies an increment of cell proliferation and an increase or a decrease of cytokines have been reported. Other workers have found inhibitory effects or no effect in the immune functions. Because of this controversy, and for the purpose of studying the mechanism by which MLT performs its functions, we evaluated its effect on murine splenocytes's proliferation after a mitogenic stimulation, and quantified the levels of IL-2 and IL-1 beta in the absence or presence of Phitohemaglutinin (PHA) in supernatants of mice splenocytes cell culture treated or not with MLT. The lymphoproliferative response was assessed using tritiated thimidine in the splenocytes of mice treated with 500 micrograms of MLT/Kg b.w. and in cell cultures containing 5, 50 and 100 micrograms MLT/mL. The production of IL-2 and IL-1 beta was detected by the ELISA test. An increase in the proliferation (p < 0.01) of spleen cells treated with 50 and 100 micrograms MLT/mL an optimal dose of PHA, was detected. The in vivo or in vitro treatment with MLT increased the levels of IL-2 and IL-1 beta in the absence or the presence of PHA, maintaining the increase in the concentration of IL-1 beta up to the to ninth day of treatment. These results suggest that MLT acts directly on cell proliferation probably by binding to high affinity receptors located on spleen cells, that stimulates the production of IL-2 and IL-1 beta giving rise to an increment of cell immunity. 相似文献
14.
Patton EA Brunet LR La Flamme AC Pedras-Vasconcelos J Kopf M Pearce EJ 《Infection and immunity》2001,69(1):589-592
An interleukin-4 (IL-4)-dependent Th2 response allows wild-type mice to survive infection with the parasite Schistosoma mansoni. In the absence of IL-4, infected mice mount a Th1-like proinflammatory response, develop severe disease, and succumb. Neither the Th1 response nor morbidity is IL-12 dependent in this system. 相似文献
15.
G N Schwartz T J MacVittie R M Vigneulle M L Patchen S D Douches J J Oppenheim R Neta 《Immunopharmacology and immunotoxicology》1987,9(2-3):371-389
Data in this report compare the number of colony-forming cells (CFC) in bone marrow from irradiated and pre-irradiated C57Bl/6J mice injected with saline or recombinant interleukin-1-alpha (rIL-1). Eight to 12 days after sublethal or lethal irradiation, there were more CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units erythroid), GM-CFC (granulocyte-macrophage colony-forming cells), and day 8 CFU-S (colony-forming units-spleen) in bone marrow from rIL-1 injected mice than from saline injected mice. Prior to irradiation, there was no increase in number of CFC in bone marrow from rIL-1 injected mice. However, as determined by sensitivity to hydroxyurea, rIL-1 injection stimulated GM-CFC into cell cycle. These results demonstrate that rIL-1 injection increases the number of CFC that survive in irradiated mice and may be a consequence of the stimulation of CFC into cell cycle prior to irradiation. 相似文献
16.
Emerging evidence suggests that certain genetic polymorphisms are associated with various sub-groups of early-onset periodontal diseases (EOP). We determined the genotype with respect to a (CA)n dinucleotide repeat polymorphism in the promoter region of the interleukin-10 gene (IL-10.G) in 72 patients with EOP and in 73 healthy individuals in order to test for possible disease associations. Some differences between the frequency of individual IL.10.G alleles in the patients groups as compared to the healthy controls were detected. For example the frequency of the IL-10.G9 allele in a clinical sub-group of the EOP patients with localised disease (L-EOP, n = 21) was 64.3% as compared to 41.8% in the controls. However, statistical analysis (Monte Carlo simulation) revealed that the differences in IL-10.G allele distribution between the healthy controls and both the EOP group and the L-EOP group were not statistically significant. We conclude that this study provides no evidence for a role of IL-10.G alleles in genetic susceptibility to EOP. 相似文献
17.
B. V. Horvth A. Falus S. Tth Cs. Szalai E. Lzr-Molnr M. Cs. Holub E. Buzs A. Nagy A. K. Fulop 《Immunology letters》2002,80(3):727-154
Interleukin-6, a multifunctional cytokine upon binding to its receptor on hepatocytes regulates production of acute phase proteins involved in local and systemic inflammation. Gene expression and biosynthesis of IL-6 and its receptor (IL-6 R/gp130) is under complex regulation. Histamine, in addition to its principal role in immediate type hypersensitivity has been described to modulate IL-6 production and expression of IL-6 receptor. In this study, the IL-6 and IL-6 receptor expression was examined in histamine deficient histidine decarboxylase (HDC) knock-out mouse model. Our data suggest that in histamine deficient mice the inducibility of IL-6 is significantly reduced, whilst more IL-6 receptor/gp130 mRNA expresses in the liver than in wild type (HDC+/+) mice. These in vivo findings confirm earlier in vitro results and emphasize the efficacy of antihistamines in local IL-6 related processes. 相似文献
18.
Role of interleukin (IL-10) in probiotic-mediated immune modulation: an assessment in wild-type and IL-10 knock-out mice
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Sheil B MacSharry J O'Callaghan L O'Riordan A Waters A Morgan J Collins JK O'Mahony L Shanahan F 《Clinical and experimental immunology》2006,144(2):273-280
While the impact of Bifidobacterium infantis 35624 and other probiotics on cytokines has been shown in established colitis, the effects of B. infantis consumption in pre-inflammation of interleukin (IL)-10 knock-out (KO) mice and on the wild-type (WT) C57Bl/6 mice have not been well demonstrated. The objective of this study was to examine cytokine responses in mucosal and systemic lymphoid compartments of IL-10 KO mice early in disease and to compare with control WT mice. Mice were fed B. infantis or placebo for 5 weeks and culled prior to the onset of chronic intestinal inflammation (12-14 weeks). The spleen, Peyer's patches and intestinal mucosa were removed and stimulated with various bacterial stimuli. Cytokine levels were measured by enzyme-linked immunosorbent assay. While basal intestinal and systemic cytokine profiles of WT and IL-10 KO mice were similar, transforming growth factor (TGF)-beta was reduced in the spleen of IL-10 KO mice. Following probiotic consumption, interferon (IFN)-gamma was reduced in the Peyer's patch of both WT and IL-10 KO mice. Alterations in IFN-gamma in the Peyer's patches of WT mice (enhancement) versus IL-10 KO (reduction) were observed following in vitro stimulation with salmonella. Differential IL-12p40, CCL2 and CCL5 responses were also observed in IL-10 KO mice and WT mice. The cytokine profile of IL-10 KO mice in early disease was similar to that of WT mice. The most pronounced changes occurred in the Peyer's patch of IL-10 KO mice, suggesting a probiotic mechanism of action independent of IL-10. This study provides a rationale for the use of B. infantis 35624 for the treatment of gastrointestinal inflammation. 相似文献
19.
Gyongyi Szabo Karen Kodys Carol L. Miller-Graziano 《Journal of clinical immunology》1991,11(6):336-344
Aberrant monocyte mediator production is pivotal in the development of posttrauma immunosuppression. We have previously shown that immunodepressed trauma patients' monocytes produce elevated interleukin-6, suggesting theirin vivo preactivation. This study confirms that preactivated patients' MØ produce greater levels of IL-6 than normals' MØ to the samein vitro FcRI stimulation. We also demonstrate the capacity of interleukin-4 to downregulate the elevated interleukin-6 production of trauma patients'in vivo preactivated monocytes. Monocyte interleukin-6 downregulation by interleukin-4 is dose dependent and occurs whether FcRI cross-linking, muramyl dipeptide, indomethacin plus muramyl dipeptide, or interferon-gamma plus muramyl dipeptide is the interleukin-6 inducing stimulus. Furthermore, interleukin-4-dependent downregulation of monocyte interleukin-6 expression is confirmed at both the supernatant and the mRNA levels. Simultaneous downregulation of posttrauma elevated monokines implies a possible therapeutic benefit of interleukin-4 for trauma patients. 相似文献
20.
Male Swiss Webster mice (25-30 g) maintained on powdered control diet, or on diets containing chlordecone (CD, 10 ppm), mirex (M, 10 ppm), or phenobarbital (PB, 225 ppm) were used in this study. At these low levels, chlorinated hydrocarbon pesticides are not toxic, they neither affect food or water consumption, nor the body weight of mice. After a 15-day dietary protocol, a single challenge dose of CHCl3 (0.1 ml/kg) was administered intraperitoneally in corn oil vehicle. Liver damage was assessed 24 hours later using serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, histopathology, and lethality. For comparison, serum enzymes were measured in a separate group of mice receiving a high dose of CHCl3 (1.0 ml/kg) alone. None of the dietary treatments alone affected any of the serum transaminases. The serum enzymes were remarkably elevated in the mice treated with CD and CHCl3. A high dose of CHCl3 (1.0 ml/kg) elevated the serum enzymes more than 10-fold over those in the mice fed normal diet receiving only the corn oil vehicle. The histopathology of the liver indicated midzonal necrosis typical of liver injury from CHCl3 and depletion of PAS positive glycogen deposits. These effects were not evident in mice treated with 0.1 ml/kg CHCl3 alone. Additional histological alterations in the livers of the CD + CHCl3 group include the degenerated cells, loss of basophilic staining characteristics, and an increased degree of cytoplasmic vacuolation. The amplification of CHCl3 hepatotoxicity by CD was also reflected by a 4.2-fold increase in lethality determined by 48-hour LD50.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献