In vitro effects of meloxicam on the number, Foxp3 expression, production of selected cytokines, and apoptosis of bovine CD25+CD4+ and CD25-CD4+ cells

The purpose of this study was to evaluate the effect of meloxicam (MEL) on selected immune parameters of bovine CD25highCD4+, CD25lowCD4+, and CD25-CD4+ cells. Peripheral blood mononuclear cells (PBMCs) collected from 12-month-old heifers were treated with MEL at a concentration corresponding to the serum level of this medication following administration at the recommended dose (MEL 5 x 10(-6) M) and at a concentration 10 times lower (MEL 5 x 10(-7) M). After 12 and 24 h of incubation with the drug, the percentage of CD25highCD4+ cells decreased; however, this disturbance was quickly reversed. Furthermore, the absolute number of CD25highCD4+ cells in the PBMC populations treated with MEL 5 x 10(-6) M for 48 and 168 h was increased. Prolonged (168 h) exposure to the drug increased the percentage of Foxp3+ cells in the CD25highCD4+ cell subpopulation. The higher dose of MEL was found to significantly increase the percentage of IFN-gamma+ cells among the CD25-CD4+ cells. These results indicated that MEL does not exert an immunosuppressive effect by depleting CD4+ cells and suppression of IFN-gamma+ production by these cells. Furthermore, IL-10 and TGF-beta production was not changed following exposure to MEL.

IFNα2b augments immune responses of cisplatin+5-fluorouracil treated tongue squamous cell carcinoma patients - A preliminary study.

Background & objectives: Interferon alpha 2b (IFNα2b) has been reported to regulate several immune functions efficiently to enhance the cytotoxic activity of NK and T cells towards various forms of tumours. The objective of the present study was to evaluate the efficacy of IFNα2b in overcoming disease induced and/or treatment associated imunosuppression of tongue squamous cell carcinoma (TSCC) patients undergoing chemotherapy for better clinical outcome. Methods: Seven TSCC patients under cisplatin + 5-fluorouracil chemotherapy in combination with IFNα2b were assessed for various immunohaematological parameters before treatment, after chemotherapy and after IFNα2b therapy. Results: Deterioration of the haematological and immune responses was detected in immunosuppressed TSCC patients after chemotherapy. IFNα2b treatment led to a recovery in these parameters in most of the patients. Greater number of T/NK cells and enhanced secretion of type 1 cytokines were also noted. Haematological complications were reduced after completion of the therapy. Immune- and haematostimulation were also observed in patients with partial response. No positive clinical response was detected in one patient. Interpretation & conclusions: IFNα2b appears to be an effective immunostimulator having clinical impact to combat the immunosuppression in TSCC patients. Successful immunostimulation by IFNα2b may help TSCC patients in clinical improvement. The findings of this preliminary study need to be confirmed on a large number of patients with TSCC.

TGF-beta-treated antigen presenting cells suppress collagen-induced arthritis through the promotion of Th2 responses

Collagen-induced arthritis (CIA) is mediated by self-reactive CD4+ T cells that produce inflammatory cytokines. TGF-beta2-treated tolerogenic antigen-presenting cells (Tol-APCs) are known to induce tolerance in various autoimmune diseases. In this study, we investigated whether collagen-specific Tol-APCs could induce suppression of CIA. We observed that Tol-APCs could suppress the development and severity of CIA and delay the onset of CIA. Treatment of Tol-APCs reduced the number of IFN-gamma- and IL-17-producing CD4+ T cells and increased IL-4- and IL-5-producing CD4+ T cells upon collagen antigen stimulation in vitro. The suppression of CIA conferred by Tol-APCs correlated with their ability to selectively induce IL-10 production. We also observed that treatment of Tol-APCs inhibited not only cellular immune responses but also humoral immune responses in the process of CIA. Our results suggest that in vitro-generated Tol-APCs have potential therapeutic value for the treatment of rheumatoid arthritis as well as other autoimmune diseases.

Conceptos emergentes de tolerancia y autoinmunidad: Nuevos enfoques terapéuticos / Tolerance and autoimmunity: Novel therapeutic approaches

La función primaria del sistema inmune es resguardar al individuo de los patógenos potencialmente dañinos que invaden el medio ambiente en el cual nos desarrollamos. Este cuenta con dos grandes ramas, la inmunidad innata y la adaptativa, ambas con la propiedad de diferenciar lo peligroso de aquello inofensivo. Estos procesos se hallan regulados por mecanismos homeostáticos que constituyen la tolerancia inmunológica, a los fines de limitar aquellos procesos prolongados y silenciar los potencialmente autoagresivos. Ante la falla de estos mecanismos de control, surgen las enfermedades autoinmunes. Avances en el conocimiento de la fisiopatología de estas entidades, han abierto un nuevo capítulo en el terreno de la inmunofarmacología. Su prometedor potencial actualmente nos ofrece novedosas herramientas terapéuticas para controlar y atenuar el daño causado por este tipo de respuestas. No obstante, debe continuarse la investigación en el campo de los agentes biológicos, ya que ninguno de ellos se encuentra libre de inconvenientes. Seguramente, futuros hallazgos se concretarán en futuros aciertos. Y los aciertos, en Medicina, equivalen a esperanza.

The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components. Failure to silence self-reactive T and B cells results in the generation of autoimmune disease. Recent advances in our knowledge of these pathological entities have opened a new chapter in the pharmacology of the immune system. Its promising potential currently offers new therapeutic agents to control and attenuate pathological tissue damage. Nevertheless, further research regarding these biologic agents is required, since they are not free from inconveniences. It is without question that upcoming findings in this field will instill hope into the quest for the "magic bullet".

Effect of AC II, a herbal formulation on radiation-induced immunosuppression in mice.

A single dose of 6 Gy irradiation significantly reduced the total WBC count while in herbal formulation (AC II) treated groups it was found to be significantly increased. Similarly bone marrow cellularity and alpha-esterase positive cells, which were lowered by radiation, were partly restored in AC II treated groups. The data indicate that AC II can overcome the immunosuppression produced by irradiation.

Treatment of patients with haemophilia and inhibitory antibodies.

The development of inhibitory antibodies is a complication which arise in approximately 10% of patients with haemophilia A. The underlying genetic mutation is the single most important predisposing cause, although other risk factors have been identified. Periodic screening for inhibitors is a vital aspect of haemophilia care. The consequences of inhibitor development are very significant in terms of morbidity and cost. Several agents are now available for control of bleeding, but these are often very expensive. The most useful agents include recombinant activated factor VII, prothrombin complex concentrates and porcine factor VIII. It is possible to suppress antibody production with immune tolerance, which is successful in approximately 85% of cases and relapse is rare.

A synergistic decline in humoral and cellular immunity of diabetic mice on exposure to polluted air.

It is clinically known that diabetic patients are more prone to infectious diseases, due to low immune status. Since, some of the common air pollutants are reported to suppress immune system, how exposure to artificially polluted air influences the immune responses in experimental diabetic mice was studied. A diabetic state was induced by alloxan and mice were exposed to artificially polluted air for 30 days. During the period of exposure, the humoral (antibody titer) and cellular (foot and swelling) immune responses to antigenic challenges with sheep RBC were investigated. The exposure to polluted air produced a significant decline in the immune responses in non-diabetic mice whereas a synergistic decline was observed in diabetic group. Since, daily oral treatment with vitamin E (150 mg/kg) significantly prevented the pollution induced immunosuppression, the involvement of free radicals is suggested.

A to Z: vitamin A and zinc, the miracle duo.

Dietary micronutrients such as vitamins and trace minerals are known modulators of host immune responses against common pathogens. In this respect, vitamin A and zinc have recently received increased attention. Several in vivo and in vitro studies suggest that vitamin A may be a critical player in the mucosal immune responses in the respiratory and gastrointestinal tracts, particularly in undernourished children. The effect may be mediated primarily by stabilization of the membrane of mucosal epithelial cells, as well as enhanced leukocyte functions. The beneficial effect of vitamin A therapy in reducing measles-associated morbidity and mortality suggests its crucial role in defenses against viral pathogens. Zinc is also known affect leukocyte functions such as phagocytosis and T-lymphocyte-mediated immune responses. However, unlike vitamin A, zinc has been investigated primarily for its effects on bacterial infections. Dietary supplementation or therapeutic treatment with vitamin A and zinc may be a cheap yet effective means of preventing or treating infections in highly susceptible populations. Additional studies, however, are required to better define the types of pathogens and the specific human populations that may benefit from such therapy.

Anti-idiotype antibodies and circulating immune complexes after immunisation with tetanus-toxoid.

OBJECTIVES: To determine if anti-idiotype antibodies and circulating immune complexes in individuals before and after immunisation with tetanus toxoid play a role in the immune response. DESIGN: A study of individuals who were administered a single dose of tetanus toxoid (TT) and who were unimmunized. SETTING: Out patient departments of a large public hospital in Bombay, India. SUBJECTS: Thirty eight individuals pre-immunisation and forty five individuals post-immunisation with tetanus toxoid, tested at 1, 3, 6, and 12 months. MAIN OUTCOME MEASURE: Development of anti-tetanus anti-idiotype antibodies and circulating immune complexes. RESULTS: Pre-immunisation cases did show presence of anti-tetanus antibodies but in lower titres than post-immunisation up to six months, after which there was a reduction. Specific anti-idiotype antibodies were detected in 19 cases. One and three months after immunisation more cases had high titre antibodies and circulating immune complexes, though after six months, there was a fall in anti-tetanus antibody titres. Circulating immune complexes were seen in those samples having anti-idiotype antibodies. CONCLUSIONS: Though a significant rise in anti-tetanus antibody anti-idiotype antibodies, protective levels in mice and circulating immune complexes are seen after immunisation with TT it lasts for six months. When followed up for a period of one year it is observed that in cases having auto anti-idiotype antibodies, the anti-tetanus antibodies are maintained for a longer period.

Effect of levamisole as an immunomodulating agent in trophoblastic lesions.

Both cell mediated immunity and humoral immunity was assessed in 16 patients of hydatidiform mole and 6 patients of choriocarcinoma. Fifty percent patients of choriocarcinoma and 11 patients of vesicular mole were given levamisole (LVM) trial and were followed for 2 months. Absolute lymphocyte count (ALC) was significantly increased in vesicular mole after levamisole treatment but in choriocarcinoma no effect was obtained. Marked improvement of T cell rosette count was also seen in LVM treated patient of both vesicular mole (p < 0.001) and choriocarcinoma. Cutaneous DTH response to 2:4 DNCB in vesicular mole was also increased after LVM. Before treatment only 31.25% patients had strong cutaneous response but after treatment 53.35% patients had strong response, while cases of choriocarcinoma were unaffected. LVM also raised all the serum immunoglobulins (IgG, IgM, IgA) in both vesicular mole and choriocarcinoma. Hence, levamisole therapy was found to have a beneficial effect on both cellular and humoral immunity in the lesions of trophoblasts.

Modulation of immunosuppression in obstructive jaundice by Tinospora cordifolia.

A clinical study was undertaken to determine the immune status of patients with obstructive jaundice. Screening of 16 patients for phagocytic and microbicidal activity of polymorphonuclear cells (PMN) revealed a significant depression (21.2 +/- 3.7% phagocytosis and 20.85 +/- 4.5% intracellular killing) of these functions, as compared to normal values (30.37 +/- 5.1% and 26.41 +/- 4.3% respectively). An animal model of cholestasis was also established, using rats, in which a significant depression of activity of PMN and peritoneal macrophages was observed. These cellular abnormalities were found to precede and predispose to infection. The rats also showed an increased susceptibility to Escherichia coli infection (mortality rate 77.78%). A defect was detected in their serum responsible for depressing the function of phagocytic cells. An attempt was made to improve this immunosuppression by treating the rats with water extract of T. cordifolia 100 mg/kg for 7 days, following development of cholestasis. The extract improved the cellular immune functions. Mortality rate following Esch. coli infection was significantly reduced to 16.67 per cent. This study showed that cholestasis results in immunosuppression and therefore indicates the need for an immunomodulator in management of obstructive jaundice. The plant T. cordifolia seems to meet this need by consolidating host defence mechanism.

Tuberculosis in patients with malignant disease.

Of 2,143 biopsy proven cancer patients seen at our hospital over a six year period, 4 (0.19%) patients developed active tuberculosis (TB) during anticancer therapy or shortly after its completion. The cancer diagnoses of those patients were non-Hodgkin's lymphoma, breast cancer, chronic myelogenous leukemia, and astrocytoma. Institution of antituberculous therapy was successful in three patients, however, the TB course was rapidly fatal in the fourth patient with non-Hodgkin's lymphoma despite therapy. The association between TB and neoplasia is emphasized. TB complicating malignant disorders represents complex problem regarding its early recognition and its managements.

Trypanosoma (herpetosoma) rangeli Tejera, 1920: the course of infection in immunosuppressed mice

Las infecciones experimentales por Trypanosoma (Herpetosoma) rangeli Tejera, 1920 muestran típicamente un repentino aumento de la parasitemia la cual, igualmente, declina y desaparece de manera abrupta e irregular. La droga cyclofosfamida fue usada para inmunosuprimir ratones albinos de 6, 16 y 26g infectados i.p. con T. rangeli de cultivo LIT. Las curvas iniciales de parasitemia fueron similares en los animales tratados y controles, pero la droga extendió el período de parasitemia patente y la repetición del tratamiento reactivó la parasitemia críptica,. Por cuanto ha sido demostrado que T. rangeli realiza un ciclo intracelular mediante multiplicación de amastigotes, es sugerido que el aumento de la parasitemia y el mantenimiento de infecciones crípticas son debidos al ciclo tisular del parásito en el cual tripomastigotes "jóvenes" reinvaden los tejidos mientras que las formas "adultas", incapaces de penetrar, predominan en sangre durante los niveles más elevados de la parasitemia de donde pueden ser tomados por el insecto vector o eliminados más tarde por la respuesta inmune adquirida del hospedador; supresión mediada por drogas de esta respuesta podría prolongar la parasitemia

Effects of Antipsychotic Drugs on Cellular lmmunity in Mice

The effects of the two antipsychotic drugs, chlorpromazine and haloperidol, the focus of this study, on cell-mediated immunity in male ICR mice. The peripheral blood WBC count decreased significantly in both cholorpromazine and haloperidol. The absolute lymphocyte count decreased only in the haloperidol-treated groups. The absolute number of thy-1-bearing cells described in both the chlorpromazine and haloperidol groups, the most remarkable effects evidencing itrself in the booster groups of higher dosage chlorpromazine (15 mg/kg), and lower and higher-dosage haloperidol (1 mg/kg and 5 mg/kg). The absolute spleen T-lymphocyte count was decreased significantly in the chlorpromazine higher-dosage booster-dose group and the haloperidol higher-dosage (5 mg/kg) single-dose group and the haloperidol lower and higher-dosage (1 mg/kg and 5mg/kg) booster-dose group. Also, chlorpromazine and haloperidol significantly impaired the in-vitro lymphocyte response to phytohemagglutinin (PHA) and produced a negative reaction of the delayed-hypersensitivity type induced by BCG vaccination. These findings suggest that chlorpromazine and haloperidol suppress the cellular immune responses in mouse.