摘要:

AbstractIt has recently been shown that inactive disaccharidic analogs of lipid A, an essential structure of lipopolysaccharide (LPS), may act as LPS antagonists which would be effective against septic shock induced by gram-negative bacteria endotoxin. In the present study we examined the inhibitory effect of DY-9973, a synthetic monosaccharidic lipid A analog, on LPS-induced cytokine expression in macrophages and lethal toxicity in mice. DY-9973 inhibited TNF-αproduction induced by LPS in human monocytes and monoblastic U937 cells. Expression of cytokine mRNAs such as TNF-αand IL-1βinduced by LPS was inhibited by treatment with DY-9973 in U937 cells. Meanwhile, DY-9973 did not inhibit IL-1β-induced TNF-αproduction in U937 cells. TNF-αproduction induced by LPS or IL-1βwas similarly inhibited by treatment with herbimycin, a tyrosine kinase inhibitor. Pretreatment with DY-9973 inhibited the elevation of serum TNF-αactivity induced by the injection of LPS and reduced the lethal toxicity of LPS in BCG-primed mice. These results suggest that monosaccharidic lipid A analog such as DY-9973 can inhibit LPS-induced activation of macrophages and that it reduces lethal toxicity of LPS.

ISSN:0892-3973    

DOI:10.3109/08923979609052749

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractWe investigated the antitumor effect of local injections with interleukin (IL)-2 in combination with an injection with mitomycin C (MMC). In BALB/c mice inoculated intraperitoneally (i.p.) with syngeneic Meth A fibrosarcoma on day 0, the i.p. injections with IL-2 at a dose of 20000U twice daily from day 7 to day 10 significantly prolonged survival of the treated mice and such treatment augmented a concomitant immunity specific for the tumor i.p. inoculated. On the other hand, the i.p. injections with IL-2 at a dose of either 5000U or 50000U resulted in no prolonged survival of the treated mice. In addition, neither intravenous nor subcutaneous injections with IL-2 at a dose of 20000U showed the prolonged survival of the treated mice. We further investigated a modulatory effect of a local injection with MMC on the IL-2-induced antitumor effect. Thein vivoantitumor effect of local injections with IL-2 was not detected when combined with a local administration of MMC, whereas a systemic administration of MMC showed no such inhibitory effect on the IL-2-induced antitumor effect. Moreover, a delayed-type hypersensitivity response against Meth A, which was augmented by the local injections with IL-2, was significantly diminished by the local administration of MMC. Collectively, our results indicate that local injections with IL-2 could elicit the antitumor effectin vivaonly when given at an optimal dose and that this effect could be rather diminished by combing with a local administration of MMC.

ISSN:0892-3973    

DOI:10.3109/08923979609052750

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractStructural analogs of the hexapeptide sequence 54–59 (A) human casein, reported to stimulate immune response, were synthesized and evaluated for immunostimulant activity. Hexapeptide 91/409 (C), 90/649 (D) and 91/361 (E) stimulated higher antibody titre and delayed type of hvper-sensitivity (DTH) response than the natural casein hexapeptide in BALB/c mice-sheep red blood cells (SRBC) and guinea pig-ovalbumin models. These peptides also induced higher stimulation of non-specific immune response as evidenced by increase in macrophage migration index (MMI), phagocytosis of (14C) lecuine labelledEscherchia coli, incorporation of (14C)-glucosamine in peritoneal macrophages and proliferative response of mouse thymocytes. Significant suppression on the course ofPlasmodium bergheiinfection was also observed on day 4, in the animals treated with hexapeptidse C and D.

ISSN:0892-3973    

DOI:10.3109/08923979609052751

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractPolymorphonuclear cell (PMN) oxidative metabolism, lymphocyte polyclonal proliferation and monocyte HLA class I antigen expression were evaluated at different intervals of time in patients with chronic hepatitis C (CH-C) subjected to a 6 month Interferonα(IFN-α) treatment and divided into Responder ('R') and Nonresponder (‘NR’) subsets according to clinical outcome.Before therapy, all subjects exhibited multiple immune alterations even if to a different extent between‘R’and‘NR’subsets: an elevated superoxide anion (O2−-) generation by suspended PMN, a failure to further increase neutrophil oxidative responsiveness under adherence conditions, an augmented phytohaemagglutin-induced lymphocyte proliferative capacity and an enhanced HLA class I antigen exression on CD14+cells. IFN-αadministration gave rise to a modulation of oxidative response in‘R’group only, since these individuals displayed an O2−-release by suspended and adherent PMN which fell within normal values. At the same time, a decrease of lymphocyte proliferation occurred in both groups of patients during IFN-αtherapy, even if it reached statistical significance in‘R’group only. Finally, a more marked difference between‘R’and‘NR’individuals was noted in terms of HLA class I antigen induction on CD14+cells at the end of therapy, as a consequence of a reduced expression of these structures in‘NR’subjects.Alltogether, these findings suggest the occurrence of a strict relationship between immunoresponsiveness and IFN-αinduced therapeutical effects in CH-C patients.

ISSN:0892-3973    

DOI:10.3109/08923979609052752

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractIn fourtheen patients in persistent vegetative state (PVS) immune responsivenes was investigated. In particular, we studied the relationship between brain lesions following traumatic injury and immune system. In this respect, phagocytosis and killing of Candida albicans by polymorphonuclear cells (PMN) and monocytes were tested. In addition serum levels of Interferon-γ(IFN-γ) were evaluated.The patients come out fiom PVS by 3–4 month were used as control group.Data shown a profound impairement of phagocytosis and killing of monocytes and low serum levels of IFNγwhen compared with normal values.Taken together, these findings suggest that brain lesions, may affect non-specific immune response.

ISSN:0892-3973    

DOI:10.3109/08923979609052753

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractImmunostimulants known to initiate cytokine production were found to inhibit processes of microsomal drug oxidation but to activate arylamine N-acetylation. The present study investigated the effects of immunstimu-lating doses of rat interferon-γ(IFNγ, 670,000 units ip) and streptolysin O (SLO, 100 HU/kg iv for 5 days) on hepatic cytosolic N-acetyltransferase (NAT) and microsomal cytochrome P450 (CYP)-dependent monooxygenases in male Wistar rats. Both IFNγand SLO activated NAT to 120% (P<0.05) and 135% (P<0.051, respectively.As expected, monooxygenases were depressed by IFNγ(P<0.05) and SLO, the ethylresorufin O-deethylase being the most susceptible enzyme. The results suggested that not only the toxin of gram-positive streptococcal bacteria SLO, but also the cytokine IFNγcan stimulate NAT activity in rat hepatic cytosol.While the enhancing SLO effect on NAT could not be neutralized by the inhibitor of transcription actinomycin D, NAT stimulation by IFNγwas abolished by actinomycin D and by the inhibitor of translation, cycloheximide. Obviously, SLO activated NAT independent of protein synthesis and different from IFNγ-mediated pathways. Posttranslational processes might be involved in NAT stimulation in the rats.

ISSN:0892-3973    

DOI:10.3109/08923979609052754

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractEmedastine difumarate (emedastine), an anti-allergic agent with anti-histaminic properties, was studied for its effect on human eosinophil chemotaxis induced by platelet activating factor (PAF). Peripheral blood eosinophils (98% purity) were obtained from healthy donors and chemotaxis assay were performed in microchemotaxis chambers. Emedastine showed a significant inhibitory effect on 10−6M PAF-induced eosinophil chemotaxis, in dose dependent fashion, at concentrations from 10−6to 10−8M. Conversely, no inhibitory effect was observed on human neutrophil chemotaxis. Pretreatment of eosinophils with Pyrilamine did not affect PAF-induced eosinophil chemotaxis. Thus emedastine appears to possess a potent and selective inhibitory effect on eosinophils chemotaxis, an action which is probably unrelated to its anti-histamine properties.

ISSN:0892-3973    

DOI:10.3109/08923979609052755

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThe direct effects of wortmannin (0 to 1280 nM) on several functions in cultured macrophages isolated from Sephadex-elicited Leghorn chicken peritonea were studied. Under concentrations not affecting cell viability, wortmannin, as low as 5 nM, inhibited lipopolysaccharide (LPS)-induced nitric oxide production (P<0.01). However, wortmannin (as high as 1280 nM) exposure 5 hours post LPS induction had no effect on nitric oxide production in macrophages, indicating a blockade of LPS-induction of a signaling pathway related to nitric oxide formation. Phorbol myristate acetate (PMA)-induced superoxide production was only inhibited (P<0.001) by concurrent exposure to 1280 nM wortmannin. Prior exposure to 160 nM and higher of wortmannin for 24 hours reduced the average number of yeast cells ingested by or attached to a single macrophage (P<0.001) and the ability of the macrophage to kill the baker's yeast (P<0.05), while wortmannin itself did not affect the yeast. These data provide direct evidence for macrophages being the target cell of wortmannin and further support the notion that impaired macrophage functions are responsible for the immunosuppressive effects of wortmannin previously observed in birds.

ISSN:0892-3973    

DOI:10.3109/08923979609052756

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor