Surgery in hematopoietic tumors

The role of surgery in the diagnosis of hematopoietic malignancies is undisputed. Many techniques to procure and examine representative tissue samples are recognized in identifying dogs and cats with these diseases. More sophisticated cytologic techniques not yet readily available would be helpful in implementing appropriate diagnostic, prognostic, and therapeutic approaches. Surgery has a limited role in the management of primary disease. The greatest limitation to surgical intervention is the systemic nature of most hematopoietic malignancies. Other limitations that can more realistically be overcome include early recognition of patients with extranodal lymphomas in Stage I disease, the increased use of surgery and radiation as adjunctive therapies for patients with regional disease, a more aggressive approach to the treatment of disease complications, and the implementation of promising experimental therapies in clinical patients of the future. The surgeon treating dogs and cats with hematopoietic malignancies must, as always, practice accepted principles of bacteriologic and oncologic asepsis and await further advances in veterinary medicine to integrate this discipline more completely with other modalities of therapy.     

Paraneoplastic disorders in dogs with hematopoietic tumors

Often overlooked in the presence of neoplasia, PNDs constitute significant clinical entities in dogs with hematopoietic tumors. They may cause morbidity and mortality in such patients, with effects more severe than those caused by the associated tumor. Accurate clinical evaluation of these disorders is important in differential diagnosis and treatment, for failure to realize that cancer can produce many clinical signs similar to those of other diseases may lead to incorrect diagnosis and delayed therapy. Early recognition of the problem underlying the PND is essential to selecting the proper therapeutic approach and maximizing the patient's chances for remission and survival. The presence of these disorders may complicate or rule out the preferred therapy in some cases of hematopoietic neoplasia, because the addition of cytotoxic drugs may worsen the existing PND, predisposing the dog to a variety of complications. Appropriate management of the PND may be of more immediate importance than treatment of the tumor. The study and recognition of PNDs in dogs with hematopoietic tumors may be valuable for a number of reasons: to facilitate early diagnosis of the tumor, for the observed abnormalities may represent tumor cell markers; to allow assessment of premalignant states; to aid in the search for metastases; to help quantify and monitor response to therapy; to aid in the evaluation of tumor recurrence or progression; to aid in identifying specific pathophysiologic processes by which cancer produces systemic effects; and to provide insight into the study of malignant transformation. Recognition of PNDs is relevant to the diagnosis and treatment of many problems in veterinary cancer medicine. With increasing emphasis on diagnosis and treatment of canine hematopoietic tumors, PNDs will be recognized with greater frequency and will assume greater importance in the therapeutic management of those patients. Research in veterinary and human cancer medicine needs to be directed toward identifying more definitively those substances and pathways that are responsible for PNDs, because therapy directed toward arresting the specific pathophysiologic processes causing the PND may offer the best approach for successful management of cancer.     

Immunomodulation and immunodeficiency

This article briefly reviews the concepts of immunodeficiency and immunomodulation as they relate to selected skin diseases in the dog and cat. Immunodeficiency states are uncommon and may be associated with a subnormal or down-regulated immune system, including humoral deficiencies, such as IgA, and abnormal lymphocyte or neutrophil function. Establishing a causal relationship between a skin disease and presumed immunodeficient state has been difficult due to the rarity of such conditions, and the limited nature of the techniques used to characterise the immune system response. Severe combined immunodeficiency in dogs is a well characterised primary immunodeficiency state involving lymphocytes; retrovirus infection in cats may lead to an acquired immunodeficient state with some association with certain dermatological conditions although it remains unclear that infection is causally linked with disease. Immunomodulation usually implies stimulating the immune system along a beneficial pathway. Such a therapeutic approach may involve a wide variety of agents, for example intravenous immunoglobulin. There are few randomised controlled trials with veterinary patients that unequivocally demonstrate beneficial responses to immunomodulatory agents. Interferons are cytokines of major interest in human and veterinary medicine for their antiviral, anti-tumour and immunomodulatory effects. The advent of veterinary-licensed products containing recombinant interferon may enable demonstration of the efficacy of interferons for conditions such as canine papillomatosis and feline eosinophilic granuloma complex. Canine pyoderma has been treated with a number of presumed immunomodulatory agents with limited success. With more detailed knowledge of the pathogenesis of pyoderma it may be possible to develop efficacious immunomodulators.     

乳酸菌与免疫调节作用

乳酸菌是人消化道区域主要的微生物菌群,并作为益生菌应用于发酵食品,特别是乳制品的生产中,膳食中提供活性乳酸菌可以防止多种疾病的发生。乳酸菌在免疫调节,保持消化道微生物菌群平衡,保护消化道感染等方面起着重要作用。本文简要介绍肠道免疫系统,乳酸菌免疫调节在抗炎、抗感染、抗肿瘤中发挥重要作用,以及免疫调节功能特性评价方法。     

益生菌对宿主机体免疫调节作用研究进展

益生菌是一类对宿主机体健康有益的低致病性或无致病性微生物。大量研究表明,益生菌能够维持宿主肠道菌群平衡,作用于肠道黏膜免疫系统,引起体液免疫和细胞免疫应答,从而调节机体的免疫功能。就益生菌的免疫调节作用途径,及其对机体体液免疫和细胞免疫的影响进行了综述。     

生长抑素的免疫调节作用研究进展

神经内分泌系统和免疫系统以相似的配基和受体建立起系统间或系统内的信息环路,从而维持机体的稳态。神经肽作为潜在的免疫调质,参与调节免疫系统的各方面功能。对神经肽生长抑素(SS)及其受体在免疫系统中的分布情况以及SS对免疫功能的调节作用进行综述,以期为探索SS的免疫调节作用机理提供理论基础。     

Immunomodulation of host responses to ectoparasite infestation--an overview

Immune reactivity stimulated by ectoparasites and other arthropods has received increased attention in recent years. It is clear that a broad range of host responses are elicited, and immune effector mechanisms appear to be active in limiting infestation with blood-feeding arthropods. Host immune responsiveness appears to be altered as a consequence of infestation by certain arthropods, and the impact of these alterations on vector-borne pathogen transmission remains to be determined. Successful techniques have been developed by a number of investigators for the artificial induction of resistance to blood-feeding arthropods. These areas are examined in this paper.     

Immunomodulation in weanling swine with dietary selenium

The capability of dietary selenium (Se) to augment the immune response was evaluated in 96 crossbred weanling swine. Six groups of 16 pigs were fed diets with Se supplemented as sodium selenite at 0, 0.3, 0.6, 0.9, 1.2, and 1.5 mg/kg. The basal diet contained 0.068 mg of Se/kg. Weight gain, feed consumption, and feed efficiency were similar for all diets. Whole blood concentrations of Se linearly increased as the dietary concentrations of Se increased. The humoral response was monitored by immunoglobulin G titers to lysozyme and ribonuclease, using an enzyme-linked immunosorbent assay. Although no significant difference in immunoglobulin G titers to either antigen was detected among diets, a similar trend in antibody response was noted. The diet with 0.9 mg of added Se/kg produced the highest antibody response to both antigens, whereas the diet with 0.3 mg of added Se/kg produced the lowest titers for both antigens. Cell-mediated immunity was evaluated in the pigs by the dermal response to phytohemagglutinin. Significant difference was not detected in pigs fed the various diets in terms of the mean diameters of their dermal reactions to phytohemagglutinin injections. Although blood concentrations of Se were increased, rate and efficiency of weight gain and humoral and cell-mediated immunity were not significantly improved by adding 0.3 to 1.5 mg of Se/kg to diets.     

Immunomodulation of caprine lentiviral infection by interleukin-16

Interleukin-16 (IL-16) is a proinflammatory cytokine produced by a variety of cells including lymphocytes, macrophages, mast cells, and eosinophils. We have shown in our previous studies increased expression of IL-16 mRNA and protein in caprine arthritis-encephalitis virus (CAEV)-infected goats blood. In this study, we determined the immunomodulatory effects of IL-16 in vitro using cells derived from CAEV infected and uninfected goats. Human recombinant IL-16 (rhIL-16) significantly increased chemotaxis of peripheral blood mononuclear cells (PBMCs) of both control and CAEV-infected goats. Pretreatment of PBMC with anti-goat CD4 monoclonal antibody inhibited IL-16-induced chemotaxis of PBMC of control and infected goats suggesting that IL-16 exerts its action in goats primarily by binding to CD4. The CAEV proviral DNA was less in caprine monocytes treated with rhIL-16 infected in vitro with CAEV. These data suggest inhibitory effect of IL-16 on viral integration. Flow cytometric studies indicated a trend toward IL-16-induced increased expression of lymphocyte activation markers. Combined with our previously reported data, these experiments suggest that increased IL-16 expression during CAEV infection may inhibit viral integration.     

甘草多糖的免疫调节和抗炎作用机制研究进展

多糖类物质是具有提高免疫力、抗病毒、抗肿瘤、抗氧化、抗炎症等广泛生理作用的生物活性成分。近年来,甘草多糖的作用受到研究人员的广泛关注,甘草多糖可以通过调节机体固有免疫、体液免疫、细胞免疫和细胞因子来增强机体免疫力,还可以通过调控机体氧化平衡、MAPK信号通路和NF-κB核因子发挥有效的抗炎作用,并具有防治骨关节炎和治疗胃炎的作用。重点阐述甘草多糖的免疫调节和抗炎作用机制,旨在为甘草多糖的进一步研究提供理论基础,并为甘草多糖的临床应用提供有价值的实践指导。     

Immunomodulation therapy for feline leukemia virus infection.

Clinically ill feline leukemia virus (FeLV)-infected cats, treated with Staphylococcus protein A (SPA) or oral interferon alpha (IFN), or both, were compared with cats treated with saline (SAL). Nine cats received SPA/SAL, nine received SPA/IFN, 10 received SAL/IFN, and eight received SAL/SAL. Twelve cats survived and completed the 100-week therapy. Significantly more owners of cats treated with SPA/SAL thought their cat's health improved during treatment compared to owners of cats treated with SAL/SAL (P=0.05, pair-wise comparison) or SPA/IFN (P=0.05, pair-wise comparison). No significant differences in body weight, temperature, hematocrit, red blood cell counts, mean corpuscular hemoglobin concentration, reticulocyte counts, white blood cell or neutrophil numbers, lymphocyte concentrations, bone-marrow cytopathology, FeLV status, survival time, activity, or appetite scores were observed. No significant differences in the owners' subjective assessment of their cat's health following treatment with SAL/IFN, SPA/IFN, or SAL/SAL were seen. Therapy with SPA as a single agent results in the owners' subjective impression of improved health of their FeLV-infected cats.     

白细胞介素21及其免疫调节研究进展

白细胞介素21(IL-21)是新近发现的一种细胞因子,主要由激活的CD4+T细胞产生。IL-21通过其受体IL-21R发挥多种生物作用。IL-21R属于I型细胞因子受体家族,与IL-2、IL-4、IL-7、IL-9和IL-15受体共同享有γ链(γc)。许多研究表明IL-21独自或与其他细胞因子协同影响多种免疫细胞的增殖、生存、分化和功能,参与对免疫反应稳态平衡的调节。为了更全面了解IL-21研究进展,论文对IL-21与IR-21R的发现、结构特征、表达分布、信号通路以及IL-21对免疫细胞的调节作用进行综述。     

Immunomodulation by virulence proteins of the parapoxvirus orf virus

Three orf virus putative virulence proteins are described that exhibit immunomodulatory functions. The OVIFNR gene at the left terminus of the viral genome encodes an interferon resistance protein with homology to the E3L gene of vaccinia virus. OVIFNR functions by preventing a dsRNA-dependent kinase from inhibiting virus and cell protein synthesis as part of the interferon-induced anti-viral state within infected cells. The orf virus orthologue of the ovine interleukin-10 (vIL-10) gene is located at the right terminus of the viral genome. Both vIL-10 and host (ovine) IL-10 function in vitro as inhibitors of pro-inflammatory cytokine production by keratinocytes and macrophages, and both inhibit IFN-gamma production from activated peripheral blood lymphocytes. Both the orf virus vIL-10 and ovine IL-10 stimulate mast cell and thymocyte proliferation. In this respect the orf virus IL-10 differs from Epstein Barr virus IL-10 which does not exhibit cell proliferative activity. Finally, the orf virus GM-CSF inhibitory factor gene (GIF) at the right terminus of the viral genome encodes an inhibitor of GM-CSF that also binds IL-2. Together, these viral proteins are capable of inhibiting key components of the ovine anti-virus immune and inflammatory response.     

粒细胞-巨噬细胞集落刺激因子基因佐剂对DNA疫苗的免疫调节作用

DNA疫苗具有制备简单,不需要蛋白质的合成、提取与纯化,免疫效果维持时间长,稳定性好,易保存等特点。但由于种与种之间免疫遗传差异,DNA疫苗往往对大动物特别是对哺乳动物的免疫效果不理想。细胞因子常作为基因佐剂用以增强DNA疫苗的免疫原性。粒细胞-巨噬细胞集落刺激因子(GM-CSF)是一个具有多项潜能的造血生长因子,在免疫反应中具有重要作用,编码GM-CSF的质粒能增强DNA疫苗的免疫效果。本文就GM-CSF的分子结构、对增强疫苗免疫原性、协同其他因子作用等方面作一综述。同时介绍了基因佐剂与目的基因表达质粒的构建方案。     

国内紫锥菊免疫调节作用研究进展

紫锥菊属植物,是原产于美洲的一类菊科野生花卉。紫锥菊以其免疫调节作用闻名于世。近年来,国内引种成功,其各种药理作用在人类、畜牧业以及水产养殖业有了广泛的研究。综述国内紫锥菊免疫调节作用在不同行业的研究进展,为紫锥菊在国内的应用提供参考。     

Immunomodulation: a means of disease prevention in stressed livestock

The ability to stimulate the immune response of cattle and pigs offers a new means of disease intervention. This review discusses current in vivo experiments that have evaluated immunomodulators in cattle and pigs. Levamisole, thiabendazole, imuthiol, avridine, isoprinosine, bovine recombinant interferon, human recombinant interleukin-2, bovine recombinant interleukin-2 and various supplemental vitamins and minerals have been used as immunomodulators in livestock with various degrees of success. Future research on immunomodulators, specific for domestic farm animals, will provide additional methods of treating immunosuppressed animals.     

Immunomodulation by probiotic lactobacilli in layer- and meat-type chickens

1. The aim of the experiments was to evaluate whether selected probiotic lactobacillus strains have different immunomodulating effects in layer- and meat-type strain chickens. 2. Humoral and cellular specific and non-specific immune responses were studied by experiments on cellular proliferation, entry and survival of Salmonella bacteria in gut and spleen leukocytes, immunoglobulin isotypes and specific immunoglobulin titres. 3. The effects of two different feeding regimes (short and continuous feeding) and doses for administration of lactobacilli were studied. 4. The lactobacillus strains that were evaluated showed modulating effects on the immune system of layer- and meat-type chickens. 5. In meat-type strain chickens the lactobacilli had a stimulating effect when the chickens were young (up to 3 weeks) and the dose was relatively high, whereas in layer-type chickens a lower effective dose and discontinuous administration was also effective. 6. Immunoprobiotic lactobacilli can have a positive effect on humoral and cellular immune responses in layer- and meat-type strain chickens, but the lactobacillus strain to be used, the age of the animals and effective dose of lactobacilli to be administered need to be optimised.     

Immunomodulation in cattle immunized with Brucella abortus strain 19

Regulation of the bovine immune response to immunization with Brucella abortus Strain 19 (S19) was investigated through application of a modification of an assay to measure suppressor T lymphocyte activities in humans and through development and characterization of antigen-stimulated T lymphocyte lines in vitro. A total of nine of steers were alloted into two groups: control (n = 4) and S19-immunized (n = 5). Peripheral blood mononuclear cells (PBMC) from each animal were cultured in vitro with mitogens (concanavalin A (Con A) and pokeweed mitogen (PWM], B. abortus antigens (B. abortus soluble antigen (BASA) and whole heat-killed B. abortus cells (HKC)) and media alone periodically from days 4 through 49 of the experiment. Supernates from these cultures were assayed for immunomodulatory activity(s) by addition to indicator cultures stimulated with suboptimal concentrations of Con A. Supernates from PBMC of S19-immunized steers generated with B. abortus antigens significantly (P less than 0.05) suppressed indicator cell responses as compared to those from control steers on days 35 and 49 post-immunization. This suppressive activity from PBMC of immunized cattle with respect to that of control cattle could also be induced through mitogenic stimulation with Con A or PWM. On day 49 of the study, suppressive activity was spontaneously released from the PBMC of immunized cattle. T lymphocyte lines were initiated from two S19-immunized steers at 2 and 9 weeks post-immunization. These T cell lines were characterized with respect to proliferative responses to B. abortus antigens through in vitro assay and surface marker expression through indirect immunofluorescence with a limited panel of monoclonal antibodies. Results from the present study indicated that S19 immunization induces a subpopulation(s) of cells in the PBMC of cattle capable of regulating the in vitro response to B. abortus. This regulatory activity is detectable by in vitro assay as early as 7 weeks post-immunization. Furthermore, the regulatory cell(s) appear to involve BoCD8+ T, lymphocytes which are specific for B. abortus antigens.