International journal of immunopharmacology最新文献

{"title":"A reduction in blood insulin levels as a host endocrine response during tumor development","authors":"Hugo Oscar Besedovsky ,&nbsp;Sigurd Normann ,&nbsp;Martin Schardt ,&nbsp;Adriana del Rey","doi":"10.1016/S0192-0561(00)00067-9","DOIUrl":"10.1016/S0192-0561(00)00067-9","url":null,"abstract":"<div><p><span>It has been previously reported that endogenous insulin levels<span> decrease during tumor growth. We have now studied whether this host endocrine response is independent of the way in which the tumor is induced. For this purpose, animals transplanted with tumor cells induced by 3-methylcholanthrene (MCA) or 7,12-dimethylbenz(a) anthracene (DMBA), or with EL-4 lymphoma cells, and animals that develop autochthonus tumors induced by MCA or the </span></span>murine mammary tumor virus<span> (MMTV) were used. These procedures result on the induction of tumors of different histologic types: fibrosarcoma<span>, mammary adenocarcinoma<span><span> and lymphoma. The results obtained showed that a reduction in insulin levels preceded the overt appearance of tumors in all models of syngeneic or autochthonus tumors studied but not when DMBA-induced tumor cells were administered into allogeneic recipients. Reduced levels of insulin before tumor detection appeared to affect the onset of MCA-induced tumors. Indeed, those mice with a late tumor onset were those that had a more pronounced decrease in </span>insulin blood levels during the induction phase of authocthonous MCA-induced tumors. Soluble factors associated with tumor growth seem to mediate the reduction in insulin blood levels in mice transplanted with EL-4 tumor cells. The results obtained indicate that the reduction in insulin levels detected is a consequence of the recognition of tumor cells by the host, and seems to be independent of the histologic type of the neoplastic cells that develop. Pharmacological interventions at the levels of mechanisms that control insulin output should clarify the relevance of decreased levels of this hormone for tumor development.</span></span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1113-1119"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00067-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21959645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Of mice and memories","authors":"James E Talmadge","doi":"10.1016/S0192-0561(00)00077-1","DOIUrl":"10.1016/S0192-0561(00)00077-1","url":null,"abstract":"","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1023-1024"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00077-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21960416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prospects for cancer gene therapy","authors":"Carla De Giovanni ,&nbsp;Patrizia Nanni ,&nbsp;Guido Forni","doi":"10.1016/S0192-0561(00)00066-7","DOIUrl":"10.1016/S0192-0561(00)00066-7","url":null,"abstract":"<div><p><span>Gene therapy is a flexible technology with which to look for new ways of inhibiting cancer. However, the marginal success achieved has made it clear that direct engineering of cancer cells is more complex than had been supposed. The main barriers are raised by the difficulty of securing gene delivery into cancer cells in vivo and the selective advantages of those against which it is ineffective. These drawbacks do not arise when an immunological approach is adopted. Genes coding for tumor-associated peptides are used to engineer professional antigen presenting cells (APC). Alternatively APC pulsed with tumor antigens<span><span> are engineered to overexpress costimulatory molecules or release cytokines. A more conservative approach is to engineer whole tumor cells with costimulatory and MHC molecules. Tumor cells can also be engineered to secrete cytokines and </span>chemokines<span><span>. The sustained presence of these factors in the tumor microenvironment recruits and activates distinct repertoires of APC and skews the antitumor response towards Th1 or Th2 reactivity. Engineered tumor cells are quickly rejected while mice acquire an </span>immune memory against subsequent challenges, even when the tumor involved is poorly immunogenic. They also cure mice bearing incipient tumors and small metastases. This efficacy, however, vanishes as the tumor progresses. Even the best-induced </span></span></span>specific immunity, therefore, is of no avail against advanced tumors. By contrast, the experimental data endorse the rational expectation that cancer vaccines will soon be both an established treatment of minimal disease after conventional management and a way of securing preventive antitumor vaccination.</p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1025-1032"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00066-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21960417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunostimulation by bacterial components: I. Activation of macrophages and enhancement of genetic immunization by the lipopeptide P3CSK4","authors":"U.v.d Esche ,&nbsp;M Ayoub ,&nbsp;S.D.C Pfannes ,&nbsp;M.R Müller ,&nbsp;M Huber ,&nbsp;K.-H Wiesmüller ,&nbsp;T Loop ,&nbsp;M Humar ,&nbsp;K.-F Fischbach ,&nbsp;M Strünkelnberg ,&nbsp;P Hoffmann ,&nbsp;W.G Bessler ,&nbsp;K Mittenbühler","doi":"10.1016/S0192-0561(00)00069-2","DOIUrl":"10.1016/S0192-0561(00)00069-2","url":null,"abstract":"<div><p><span><span>Synthetic lipopeptides derived from the N-terminus of bacterial </span>lipoprotein<span> constitute potent macrophage activators and polyclonal B-lymphocyte stimulators. They are also efficient immunoadjuvants in parenteral, oral and nasal immunization either in combination with or after covalent linkage to an antigen. Here we show how alterations in the molecular structure influence their biological properties indicating P</span></span>₃CSK₄<span><span> as one of the most active members of a lipopentapeptide fatty acid library. This compound resulted in a most pronounced macrophage stimulation as indicated by NO release, activation of NFκB translocation, and enhancement of tyrosine </span>protein phosphorylation. Furthermore, P</span>₃CSK₄<span> activates/represses an array of at least 140 genes partly involved in signal transduction and regulation of the immune response. Finally we have evidence that P</span>₃CSK₄<span> constitutes an effective adjuvant for DNA immunizations, especially increasing weak humoral immune responses<span>. Our findings are of importance for further optimizing both conventional and genetic immunization, and for the development of novel synthetic vaccines.</span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1093-1102"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00069-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21959643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage activation by antiviral acyclic nucleoside phosphonates in dependence on priming immune stimuli","authors":"Z Zı́dek ,&nbsp;D Franková ,&nbsp;A Holý","doi":"10.1016/S0192-0561(00)00068-0","DOIUrl":"10.1016/S0192-0561(00)00068-0","url":null,"abstract":"<div><p><span><span>Acyclic nucleoside </span>phosphonates<span> (ANPs) are potent broad-spectrum antivirals, also effective against immunodeficiency viruses and hepatitis viruses. Effects of several ANPs on in vitro cytokine gene expression and nitric oxide (NO) production by murine peritoneal macrophages were investigated. Included in the study were 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA; Adefovir), 9-(</span></span><em>R</em>)-[2-(phosphonomethoxy)propyl]adenine [(<em>R</em>)-PMPA; Tenofovir], 9-(<em>S</em>)-[2-(phosphonomethoxy)propyl]adenine; (<em>S</em>)-PMPA), 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP), 9-(<em>R</em>)-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), and 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG). Some of them, i.e. (<em>R</em>)-PMPA, (<em>S</em><span>)-PMPA, and PMEG, stimulate secretion of TNF-α and IL-10 in a concentration-dependent manner, and enhance the IFN-γ-induced secretion of TNF-α. Although unable to activate production of nitric oxide (NO) on their own, these compounds substantially augment NO formation induced by IFN-γ. Analysis of the expression of inducible NO synthase<span> mRNA indicates that the NO-enhancing effect of ANPs is mediated posttranscriptionally. In contrast to IFN-γ, production of NO triggered by lipopolysaccharide<span> (LPS) alone, or synergistically by LPS+IFN-γ, remains unaltered by ANPs. The immunomodulatory effects have been differentially expressed in distinct genotypes of inbred strains of mice, including the low NO-responders Balb/c and high NO-responders C3H/HeN. Although less effectively, PMEG and (</span></span></span><em>R</em>)-PMPA also increase production of TNF-α and NO by the IFN-γ- but not LPS-co-stimulated macrophages from C3H/HeJ mice, which are otherwise hypo-responsive to major immune stimuli provided by IFN-γ and LPS. It can be concluded that the expression of immunomodulatory properties of ANPs depends on the immune state of cells and its activation by distinct priming signals.</p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1121-1129"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00068-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21958422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel tumor necrosis factor-α inhibitory protein, TIP-B1","authors":"Erica S Berleth,&nbsp;Alicia D Henn,&nbsp;Hira L Gurtoo,&nbsp;Robert Wollman,&nbsp;James L Alderfer,&nbsp;Enrico Mihich,&nbsp;M.Jane Ehrke","doi":"10.1016/S0192-0561(00)00071-0","DOIUrl":"10.1016/S0192-0561(00)00071-0","url":null,"abstract":"<div><p>TIP-B1, a novel TNF inhibitory protein, has been identified, purified and characterized from cytosolic extracts of TNF-treated human fibroblasts, and a partial TIP-B1 cDNA clone has been obtained. The (27 kDa p<em>I</em><span>≈4.5 TIP-B1 protein is unique based on both the sequence of three internal peptides (comprising 51 amino acids), and the nucleotide sequence<span> of the corresponding cDNA clone. TNF-sensitive cells, when exposed to TIP-B1 prior to the addition of TNF, are completely protected from TNF-induced lysis. Thus, this TIP-B1 treatment effectively makes these cells TNF-resistant. Furthermore, TIP-B1 protects cells from apoptotic lysis induced by TNF. TIP-B1 does not interfere with the interactions between TNF and the TNF receptors<span> based on flow cytometric analysis of the cellular binding of biotinylated TNF. These and other data indicate that TIP-B1 is not a soluble TNF receptor, nor an anti-TNF antibody, nor a protease that degrades TNF, yet TIP-B1 functions when added exogenously to cells. Thus, TIP-B1 is not one of the proteins previously reported to be involved in resistance to TNF. The fact that incubation of the newly discovered novel TIP-B1 with TNF-sensitive cells protects them from TNF-induced cell death, including TNF-mediated apoptosis, makes TIP-B1 a candidate for therapeutic modulation of TNF-induced effects.</span></span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1137-1142"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00071-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21958424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of immune dysfunction in stem cell transplantation","authors":"James E Talmadge ,&nbsp;Rakesh Singh ,&nbsp;Kazuhiko Ino ,&nbsp;Ana Ageitos ,&nbsp;Suleyman Buyukberber","doi":"10.1016/S0192-0561(00)00078-3","DOIUrl":"10.1016/S0192-0561(00)00078-3","url":null,"abstract":"<div><p><span>High dose therapy (HDT) and stem cell transplantation<span> (SCT) results in alterations in the immunologic network, thymic re-education and the induction of peripheral tolerance. The changes to the immunoregulatory cascade and tolerance induction associated with autotransplants have been investigated in a series of studies focused on leukocyte reconstitution and function following HDT and autologous SCT. In these studies, we observed a significant decrease in the CD4:CD8 T cell ratio post-transplantation compared to normal peripheral blood (PB) donors due to a decrease in CD4</span></span>⁺<span><span> cells. In addition, T cell function (phytohemagglutinin (PHA) mitogenesis) was consistently depressed compared to samples obtained from normal PB donors. The loss of T cell function was associated with an increased frequency of circulating monocytes, their expression of </span>Fas ligand (FasL) and a high frequency of apoptotic CD4</span>⁺ T cells. Indeed, 28–51% of circulating CD4⁺ T cells were observed to be apoptotic during the first 100 days following HDT and SCT. These studies suggest that ‘primed’ or activated Fas⁺ CD4⁺ lymphocytes interact with FasL⁺ monocytes, resulting in apoptosis, leading to the preferential deletion of CD4⁺<span> T cells, a decrease in the CD4:CD8 T cell ratio and depressed T cell function. Further, as discussed herein, the T cells are activated with a predominantly type 2 phenotype, which may also contribute to the maintenance of the immunosuppressive<span> condition. Therefore, there is the potential to regulate immune recovery by stem cell product manipulation or post-transplantation cytokine administration.</span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1041-1056"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00078-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21959638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer drugs plus cytokines: immunodulation based therapies of mouse tumors","authors":"E Mihich,&nbsp;M.J Ehrke","doi":"10.1016/S0192-0561(00)00072-2","DOIUrl":"10.1016/S0192-0561(00)00072-2","url":null,"abstract":"<div><p>As demonstrated in this laboratory, several cytotoxic anticancer agents<span><span><span> have immunomodulating effects at relatively low doses and, in combination with non-toxic doses of certain cytokines, can exert immunity-dependent curative effects in mouse tumor models. Thus, adriamycin<span> (Dox) has been shown to enhance the activation of macrophages with associated increases of IL1 and </span></span>TNF production, to stimulate the production of </span>IL2<span><span> and the development and action of CTLs. In the EL4 lymphoma C57BL/6 mouse model, combinations of appropriate regimens of Dox plus IL2 or TNF induce cures and the long-term survivors exhibit life-long immunological memory. Combinations of </span>cyclophosphamide<span> plus TNF have analogous effects. In the E0771 breast tumor C57BL/6 mouse model, Dox plus TNF at doses which are without antitumor activity when given alone, cause complete cures of established tumors with concomitant stimulation of CTL and NK cells responses. The mechanisms involved in these therapeutic responses are discussed. In conclusion, the results obtained substantiate the possibility of establishing antitumor curative combination regimens based on the utilization of low non-toxic immunomodulating doses of certain anticancer drugs and specific cytokines.</span></span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1077-1081"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00072-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21959641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunostimulation by bacterial components: II. Efficacy studies and meta-analysis of the bacterial extract OM-89","authors":"M Huber ,&nbsp;K Krauter ,&nbsp;G Winkelmann ,&nbsp;H.W Bauer ,&nbsp;V.W Rahlfs ,&nbsp;P.A Lauener ,&nbsp;G.S.S Bleßmann ,&nbsp;W.G Bessler","doi":"10.1016/S0192-0561(00)00070-9","DOIUrl":"10.1016/S0192-0561(00)00070-9","url":null,"abstract":"<div><p><span>The bacterial extract OM-89 (Uro-Vaxom®) consisting of immunostimulating components derived from 18 </span><em>Escherichia coli</em><span> strains is used for the treatment of recurrent urinary tract infections<span>. We investigated in the mouse the immunogenicity<span><span> of the bacterial extract after oral administration. After repeated administration<span> of OM-89, a specific serum IgG and IgA response against a number of bacterial strains was obtained. Supernatants of cell cultures prepared from the urogenital tract of immunized mice also contained increased levels of strain specific IgG and IgA. We could show a bias towards a Th1 type immune response as indicated by increased </span></span>IgG2a<span> levels in sera, and increased IFNγ levels in supernatants of spleen cells. These findings may contribute to an understanding of the therapeutic effect of Uro-Vaxom®: the metaanalysis of several clinical studies confirmed that Uro-Vaxom® constitutes an effective prophylaxis for urinary tract infections.</span></span></span></span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1103-1111"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00070-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21959644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotoxicology: role of inflammation in chemical-induced hepatotoxicity","authors":"Michael I Luster,&nbsp;Petia P Simeonova,&nbsp;Randle M Gallucci,&nbsp;Joanna M Matheson,&nbsp;Berran Yucesoy","doi":"10.1016/S0192-0561(00)00073-4","DOIUrl":"10.1016/S0192-0561(00)00073-4","url":null,"abstract":"<div><p><span><span>The liver, which is the major organ responsible for the metabolism of drugs and chemicals, is also the primary target organ for many toxic chemicals. Increasing evidence has indicated that inflammatory processes are intimately involved in chemical-induced hepatotoxic processes, and like other inflammatory diseases, such as autoimmunity, are responsible for producing mediators which can effect liver damage or repair. This review will summarize the authors’ current understanding of how inflammatory processes influence hepatic pathology and repair following exposure to established hepatotoxic chemicals including </span>carbon tetrachloride (CCl</span>₄<span>), an industrial chemical, and acetaminophen (APAP), a widely used analgesic.</span></p></div>","PeriodicalId":14002,"journal":{"name":"International journal of immunopharmacology","volume":"22 12","pages":"Pages 1143-1147"},"PeriodicalIF":0.0,"publicationDate":"2000-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0192-0561(00)00073-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21958425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}