Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord / 亚洲男科学杂志(英文版)

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.

Immunomodulatory activity of methanolic extract of morus alba linn. [Mulberry] leaves

The leaves of Morus alba Linn. [Family: Moraceae] commonly known as mulberry are mainly used as food for the silkworms and they are sometimes eaten as vegetable or used as cattle fodder in different parts of the world. The effect of Morus alba on the immune system was evaluated by using different experimental models such as carbon clearance test, cyclophosphamide induced neutropenia, neutrophil adhesion test, effect on serum immunoglobulins, mice lethality test and indirect haemagglutination test. Methanolic extract of Morus alba was administered orally at low dose and high dose of 100 mg/kg and 1 g/kg respectively and Ocimum sanctum [100 mg/kg, po] was used as standard drug. Morus alba extract in both doses increased the levels of serum immunoglobulins and prevented the mortality induced by bovine Pasteurella multocida in mice. It also increased the circulating antibody titre in indirect haemagglunation test. On the other hand, it showed significant increase in the phagocytic index in carbon clearance assay, a significant protection against cyclophosphamide induced neutropenia and increased the adhesion of neutrophils in the neutrophil adhesion test. Hence, it was concluded that Morus alba increases both humoral immunity and cell mediated immunity

Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg), an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05) and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05), catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05) and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05) showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05), and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05) and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05) response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05) suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05) suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally) with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

Melatonin treatment prevents modulation of cell-mediated immune response induced by propoxur in rats.

The effect of melatonin, a major secretory product of the pineal gland, in attenuation of propoxur (2-isopropoxy phenyl N-methyl carbamate)-induced modulation of cell-mediated immune (CMI) response was studied in rats. Male Wistar albino rats were exposed to propoxur (a widely used pesticide) orally (10 mg/kg) and/or melatonin (10 mg/kg) orally for 4 weeks. CMI was measured by delayed-type hypersensitivity (DTH), leucocyte and macrophage migration inhibition (LMI and MMI) responses and estimation of cytokines TNF-alpha and IFN-gamma levels. Rats exposed to propoxur for 4 weeks showed significant decrease in DTH, LMI and MMI responses. Propoxur also suppressed TNF-alpha and IFN-gamma production significantly. Administration of melatonin alone caused a significant increase in DTH response. Although there were no changes in the LMI and MMI response, the cytokine levels were significantly increased, as compared to control. Co-administration of melatonin along with propoxur significantly nullified the effect of the pesticide on the CMI response, except DTH and reversed levels of cytokines to near control/normal values. Thus, melatonin treatment considerably attenuated immunomodulation caused by sub-chronic treatment of propoxur in experimental animals.

Beneficial effects of Lagenaria siceraria (Mol.) Standley fruit epicarp in animal models.

Lagenaria siceraria (Mol.) Standley fruit (bottle gourd), a commonly used vegetable in India is described as cardiotonic and as a general tonic in Ayurveda. Keeping in view the presence of free radical scavenging activity in L. siceraria and involvement of free radicals in the development of various disorders, present studies were designed to evaluate the ethanolic extract of L. siceraria fruit against the disorders where free radicals play a major role in pathogenesis. The extract was found effective as hepatoprotective, antioxidant, antihyperglycemic, immunomodulatory, antihyperlipidemic and cardiotonic agent. The results showed that the radical scavenging capacity of L. siceraria fruit may be responsible for various biological activities studied.

Effect of centchroman on cellular and humoral immunity.

Centchroman (Ormeloxifene) is a nonsteroidal selective estrogen receptor modulator that is used as once a week oral contraceptive agent. The effect of centchroman on the immune system was evaluated by using different experimental models such as carbon clearance test, cyclophosphamide induced neutropenia, neutrophil adhesion test, effect on serum immunoglobulins, mice lethality test and indirect haemagglutination test. The first three models namely carbon clearance test, cyclophosphamide induced neutropenia and neutrophil adhesion test were used to study cell mediated immunity while the latter three models were used to see the effect on humoral immunity. Centchroman was administered orally at a dose of 5 mg/kg and levamisole (2.5 mg/kg/ p.o) was used as standard drug. Centchroman significantly increased the levels of serum immunoglobulins and also prevented the mortality induced by bovine Pasteurella multocida in mice. It also increased significantly the circulating antibody litre in indirect haemagglunation test. However, it did not show any significant effect on phagocytic index in carbon clearance assay and nor did influence the adhesion of neutrophils in the neutrophil adhesion test. Centchroman was also not effective in preventing the cyclophosphamde induced neutropenia. Hence, it was concluded that centchroman increases humoral immunity with no significant effect on cell mediated immunity.

Immunotoxic effects of lambda-cyhalothrin in rabbits

The effect of Lambda-cyhalothrin on the immune response was studied in rabbits exposed to the insecticide via food at concentrations of 1373.23, 686.76 or 343.38 ppm [equivalent to 1/10[th], 1/20[th] and 1/40[th] oral LD50, respectively] for 8 weeks. The humoral immune response was measured by determination of the antibody titre against sheep red blood cells [SRBC], a T - cell dependent antigen. Moreover, the cell-mediated immune response was evaluated by the delayed - type hypersensitivity reaction to tuberculin. The chemical treatment resulted in a dose - dependent suppression of both humoral and cellmediated immune responses as evidenced by decreased serum hemolysin titres and inhibition of the delayed-type hypersensitivity reaction to tubercluin, respectively. In addition, leucopenia, lymphopenia, depletion of lymphoid cells in the white pulps of spleen, mesentric lymph nodes and Peyer's patches and severe atrophy of thymus cortex were recorded. The serum total protein, albumin, globulin [specially gamma globulin], albumin/globulin [A/G] ratio and the organ to body weight ratios for spleen and thymus were significantly decreased with increasing the insecticide dosage. Moreover, different pathological alterations in liver, and brain were also observed. In conclusion, Lambdacyhalothrin exposure suppressed both humoral and cell-meditated immune responses in rabbits at the tested concentrations in a dose - dependent manner

Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts.

Centella asiatica (CA) and Rhinacanthus nasutus (RN )have been used for treatment of various illnesses, but the mechanisms of action remain largely unknown. This study focused on the influence of CA and RN extracts on cell-mediated and humoral immune responses. In human peripheral blood mononuclear cells (PBMCs), CA (water extract) and RN (water and ethanol extracts) significantly increased proliferation and the production of IL-2 and TNF-alpha. In contrast, an ethanol extract of CA inhibited human PBMC mitogenesis and the production of IL-2 and TNF-alpha. BALB/c mice treated with CA extracts (100 mg/kg bw) showed higher responses to both primary and secondary antibodies against BSA when compared with non-treated group. Only the secondary antibody response was increased in RN extract-treated mice. The present study revealed immunomodulating activity of CA and RN extracts with regard to both non-specific cellular and humoral immune responses. The data available to date suggest that they may have chemopreventive or anticancer potential.

Lymphocyte subset analyses in healthy adults vaccinated with yellow fever 17DD virus

In this study the kinetics of humoral and cellular immune responses in first-time vaccinees and re-vaccinees with the yellow fever 17DD vaccine virus was analyzed. Flow cytometric analyses were used to determine percentual values of T and B cells in parallel to the yellow fever neutralizing antibody production. All lymphocyte subsets analyzed were augmented around the 30th post vaccination day, both for first-time vaccinees and re-vaccinees. CD3+ T cells increased from 30.8 percent (SE ± 4 percent) to 61.15 percent (SE ± 4.2 percent), CD4+ T cells from 22.4 percent (SE ± 3.6 percent) to 39.17 percent (SE ± 2 percent) with 43 percent of these cells corresponding to CD4+CD45RO+ T cells, CD8+ T cells from 15.2 percent (SE ± 2.9 percent) to 27 percent (SE ± 3 percent) with 70 percent corresponding to CD8+CD45RO+ T cells in first-time vaccinees. In re-vaccinees, the CD3+ T cells increased from 50.7 percent (SE ± 3 percent) to 80 percent (SE ± 2.3 percent), CD4+ T cells from 24.9 percent (SE ± 1.4 percent) to 40 percent (SE ± 3 percent) presenting a percentage of 95 percent CD4+CD45RO+ T cells, CD8+ T cells from 19.7 percent (SE ± 1.8 percent) to 25 percent (SE ± 2 percent). Among CD8+CD38+ T cells there could be observed an increase from 15 to 41.6 percent in first-time vaccinees and 20.7 to 62.6 percent in re-vaccinees. Regarding neutralizing antibodies, the re-vaccinees presented high titers even before re-vaccination. The levels of neutralizing antibodies of first-time vaccinees were similar to those presented by re-vaccinees at day 30 after vaccination, indicating the success of primary vaccination. Our data provide a basis for further studies on immunological behavior of the YF 17DD vaccine.

Time dependent immunomodulatory response of exogenous melatonin to killed Pasteurella multocida (P52 strain) vaccine in albino rats.

The effect of time of administration of exogenous melatonin (M) at the rate of 100 microg/Kg BW of rat/day for 14 days on immunomodulation to killed Pasteurella multocida (P52 strain) vaccine (KPMV) was investigated in male albino rats during spring season with photoperiod of LL 13: DD 11 h and 25 +/- 2.5 degrees C air temperature and 70 +/- 4% relative humidity. The experiment was conducted at an altitude of 172 mts above mean sea level at latitude 28.20 degrees north, longitude 79.24 degrees east (Bareilly, U.P. India). The experimental animals were divided in-groups of 8 rats each, as KPMV + M at 4.00 h; KPMV + M at 16.00 h; KPMV and their controls M4, M16, PBS respectively. Humoral immune response was monitored at weekly intervals by an indirect ELISA and cellular immunity by leukocyte migration inhibition test (LMIT) and delayed type of hypersensitivity (DTH). As evinced by in-vitro assays and in-vivo protection studies, both humoral and cellular immune responses to KPMV were augmented in rats receiving exogenous melatonin at 4.00 h as compared to slightly reduced responses in rats treated with melatonin at 16.00 h. It was concluded that the circadian timings of melatonin administration modulate immune response in rats.

Influences of DTC and zinc supplementation on the cellular response restoration in restrained mice

The studies were conducted on Balb/c mice exposed to restraint stress twice for 12 h at 24 h intervals. Prior to restraint stress the mice were treated with sodium diethyldithiocarbamate (DTC) i.p. at a dose of 20 mg/kg five times at 48 h intervals. DTC was used per se or with zinc ions interaction, by adding zinc sulfate to drinking water at a dose of 72 microgram/mouse daily. The results obtained in the study show that restraint stress causes involution of lymphatic organs, decreased the percentage of immature (CD4+CD8+) and, mature (CD4+) thymocytes and CD4+, CD8+and CD19 + splenocytes and proliferative response of thymocytes stimulated in vitro with concanavalin A (Con A) and phytohemagglutinin (PHA). The restraint stress decreased also interleukin-1 (IL-1) production by murine intraperitoneal macrophages stimulated in vitro with lipopolysaccharide (LPS) from E. coli. Pretreatment with DTC counteracted restraint stress-induced immunosuppression, which is expressed as partial normalisation of the total number of thymocytes, splenocytes and IL-1 production, accelerated regeneration of thymus and spleen, shorter suppressive action of restraint stress on the percentage of CD4+CD8+thymocytes and in total normalisation of the CD4+thymocytes and splenocytes. DTC administered prior to restraint stress augmented the proliferative response of thymocytes to two mitogens. The immunocorrecting action of DTC is enhanced by zinc supplementation, expressed in the increased percentage of CD4+thymocytes and splenocytes, CD19 + splenocytes, proliferative activity of thymocytes stimulated with PHA and IL-1 production. The obtained results show that DTC administration can be supplemented with zinc in order to restore the immune system impaired by stress.

Humoral and cellular immunomodulation induced by propoxure in C57-w/6 mice

Propoxure [PPX] is a well-known carbamate insecticide, which has been used for several decades in the world and Iran in agriculture and public health programs. However, there is no clear investigation toward its immunotoxicity as yet. In this study, we examined the effects of subchronic i.p. exposure of PPX on humoral [PFC and HA] and cellular [DTH] responses, and also monitored T-Cell subtypes using FACS technique. Briefly, female C57b1/6 inbred mice were administered PPX [0.2, 2 and 10 mg/kg/day i.p. [5 inj/wk] for 28 days] or positive and negative controls. On the day 28, mice were examined for DTH, PFC and HA responses to SRBC. Splenocyte single cell suspension was used for measuring the spleen CD4/CD8 percentage and absolute number. In vitro lymphocyte proliferation response to non-specific antigen [PHA] was also measured using MTT method. Results showed that PPX at 10 mg/kg/day could suppress DTH response and could increase the spleen CD4-/CD8+ T-cell percentage. On the other hand, PPX at medium dose [2 mg/kg] could increase the antibody formation response against SRBC as determined by PFC and HA. Subchronic PPX at low dose [0.2 mg/kg/day] could not show any significant effects on humoral or cellular responses. It could be concluded that, subchronic PPX at high dose [10 mg/kg], possessed cellular immunosuppressive effect. However, PPX at 2 mg/kg does not change cellular response to antigen but can stimulate humoral responses. It seems that PPX has no adverse effects on mice immune system at low doses as 0.2 mg/kg, which is 10 fold greater than PPX Allowed Daily Intake limit

Attenuation of the effect of progesterone and 4'-chlordiazepam on stress-induced immune responses by bicuculline.

The present study investigates the effect of progesterone, a pregnane precursor of neurosteroids, and 4'-chlordiazepam (4'-CD), a specific ligand for mitochondrial diazepam binding inhibitor receptor (MDR) involved in neurosteroidogenesis, on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses. RS produced a significant reduction in anti-sheep red blood cells (SRBC) antibody titre, a measure of humoral immune response, and % leucocyte migration inhibition (LMI) and foot-pad thickness test, measures of cell-mediated immune responses. These effects of RS on immune responses were effectively blocked by pretreating the animals with progesterone (10 mg/kg, sc) or 4'-CD (0.5 mg/kg, sc) administered just before subjecting the animal to RS. The effect of both progesterone and 4'-CD on RS-induced immune modulation was significantly attenuated by bicuculline (2 mg/kg, ip) but not by flumazenil (10 mg/kg, ip). Unlike its effect on RS-induced immune responsiveness, progesterone (5, 10 mg/kg, sc) when administered to non-stressed animals produced a significant suppression of both humoral and cell-mediated immune responses which was not reversed by bicuculline. However, 4'-CD failed to modulate immune response in naive non-stressed animals. These results suggest that progesterone and 4'-CD affect stress-induced immune responses by modulating GABA-ergic mechanism. However, GABA-A receptor system does not appear to be involved in progesterone-induced immunosuppression in nonstressed animals.

Effect of minocycline and tetracycline on immunological responses in experimental animals.

In recent years, there has been an increase in the use of antibiotics, primarily tetracycline anlogues, like minocy cline to treat rheumatoid arthritis. However, the mechanism of action of these analogues is not clearly defined. The present study investigates the effects of minocycline and tetracycline on some immunological parameters in Wistar rats and Swiss albino mice. Haemagglutination (HA) titre was employed as parameter of humoral immune response and % leukocyte migration inhibition (% LMI) and footpad thickness tests were used as measures of cell mediated immune response. Both minocycline and tetracycline significantly improved humoral immune response in rats as indicated by an increase in anti-SRBC antibody titre. In the LMI test, depending on the time period of drug administration, there was an increase or a decrease in the % LMI. When drugs were administered on days 1-7 after sensitization, both the compounds caused a significant increase in % LMI. However, the % LMI was significantly decreased when the drugs were administered on days 7-13 of sensitization, indicating variable effects of these agents on the Immune mechanism depending on the time of administration in relation to the development of immune responsiveness. Both minocycline as well as tetracycline produced a significant decrease in the paw volume in the footpad-thickness test which indicates a decrease in lymphokine production/release. The present study thus shows that minocycline and tetracycline exhibit immunomodulatory properties, which may contribute significantly to their beneficial effects in rheumatoid arthritis.

Immunopotentiating activity of abrin, a lectin from Abrus precatorius Linn.

A non-toxic dose of abrin, (1.25 microg/kg body wt) consecutively for five days in normal mice stimulated specific humoral responses. A noticeable increase was observed in total leucocyte count, lymphocytosis, weights of spleen and thymus, circulating antibody titre, antibody forming cells, bone marrow cellularity and alpha-esterase positive bone marrow cells. The results suggest that abrin can potentiate the humoral immune response of the host.

Revisäo: efeitos imunomoduladores da vitamina D / Revision: immunomodulator effect of vitamin D

A forma ativa da vitamina D apresenta efeitos imunomoduladores observados sobre a populaçäo de linfócitos,macrófagos e células citotóxicas naturais (natural Liller) e sobre a produ135132o e a açäo de citocinas tanto in vivo quanto in vitro. Esses efeitos säo observados em modelos experimentais de doençäas autoimunes através da melhora clínica e histológica das lesöes, em neoplasias, nas quais verifica-se a reduçäo do volume de tumores sólidos, e em transplantes, com o aumento da sobrevida dos enxertos, o que torna a vitamina D um possível imunossupressor para futura utilizaçäo clínica

Possible role of histamine receptors in the central regulation of immune responses.

The present study was designed to delineate the role of H1- and H2-histamine receptors in the neuro-immune regulation in rats. The effects of H1- and H2-receptor antagonists on humoral and cell-mediated immune (HI and CMI) responses were investigated after intraperitoneal (i.p.) and intra-cerebroventricular (i.c.v.) administration. HI response was assayed by anti-sheep red blood cell (SRBC) antibody titre in presence and absence of 2-mercaptoethanol (2-ME). The CMI responses were evaluated by delayed type hypersensitivity (DTH) reaction (in vivo), i.e., measurement of footpad thickness, and lymphokine activity such as leucocyte migration inhibition (LMI) test (in vitro). On i.p. administration, both H1- (pheniramine and astemizole) and H2-receptor antagonists (ranitidine and cimetidine) were observed to produce significant enhancement of anti-SRBC antibody response. However, only H2- and not H1-receptor blockers were observed to stimulate CMI response significantly. When administered by icv route, only H2-receptor antagonists caused a statistically significant increase in both HI and CMI responses, while the H1-receptor blockers failed to modify the same. Thus, H2-receptors appear to play a major role in the histaminergic mechanisms involved in immunomodulation both at the level of immunocompetent cells active in the peripheral tissues as well as through the central nervous system structures involved in the central regulation of neuro-immune interaction.

Increase cellular immunity by using G-CSF for treatment of zoonotic dermatophytoses

In this study, 50 skin scrapings were taken from cattles as well as 20 samples were collected from the skin of human who had a contact with these animals. The percentage of T. verrucosum var. discoides isolated from cattles was 40%. The percentage of T. verrucosum var. discoides isolated from individual cases with a contact with cattle was 60%. In conclusion, WBCs counts were 5.5 Thos./UL at zero time and were increased to 26.4 after ten days during treatment, then increased to 59.2 Thos/UL after ten days of daily treatment, but the count was decreased to 35.1 Thos/UL when the cattle was clinically cured

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.