Inhibition of MCP-1 and MIP-2 chemokines in murine trichinellosis: effect of the anti-inflammatory compound L-mimosine

Mimosine is a plant amino-acid which has been reported to block DNA replication in mammalian cells and to arrest cell reversibly towards the end of the G1 phase or at the beginning of the S phase. In this study, 42 mice were infected with T. spiralis a nematode parasite, and treated with the anti-inflammatory compound L-mimosine, to determine if any alteration in the chronic inflammatory state occurred, by investigating the hosts immunological response. MCP-1, a C-C chemokine and MIP-2, a C-X-C chemokine were tested and calculated in the sera of infected animals, after 1, 10, 20, 30, 40, 50 and 60 days post infection, by ELISA method. The diaphragm and the masseters of the infected mice, were tested for inflammatory response. Here we found, that MCP-1 was partially inhibited by L-mimosine, while MIP-2 was totally inhibited. Moreover in sections of the diaphragm and masseters, the infiltration of inflammatory cells, such as macrophages, lymphocytes and eosinophils were more intense in untreated animals compared to those treated with L-mimosine. These findings show, that L-mimosine may have an inhibitory effect on MCP-1 and MIP-2 serum levels in Trichinellosis and may influence the recruitment of inflammatory cells and the intensity of the inflammatory reaction in this parasitic disease.     

Effect of the compound L-mimosine in an in vivo model of chronic granuloma formation induced by potassium permanganate (KMNO4)

The plant amino acid L-mimosine has recently been suggested to inhibit cells at a regulatory step in late G1 phase before establishment of active DNA replication forks. In addition, L-mimosine is an extremely effective inhibitor of DNA replication in chromosomes of mammalian nuclei. In this work, the effect of L-mimosine on chronic inflammation induced by dorsal injections of 0.2 ml of a 1:40 saturated crystal solution of potassium permanganate in mice, was studied. Seven days afterwards, all mice developed a subcutaneous granulomatous tissue indicative of chronic inflammatory response at the site of infection. The intraperitoneal administration of L-mimosine (200 microg/dose) to the potassium permanganate treated mice for 5 consecutive days (the first at the same time of inoculation of the KMnO4), produced a significant decrease in size and weight of the granuloma when compared to mice not treated with L-mimosine (controls). In addition, in all mice treated with L-mimosine, there was a strong inhibition of tumor necrosis factor alpha that was revealed in the serum (P<0.05) and in the minced granulomas. Interleukin-6 was not detected in the serum of treated and untreated mice. These findings show for the first time, that L-mimosine may have an anti-inflammatory effect on chronic inflammation and an inhibitory effect on tumor necrosis factor alpha and interleukin-6 generation in supernatant fluids of minced granulomas.     

Generation of TNFα, IFNγ, IL-4, IL-6 and IL-10 in Trichinella spiralis infected mice: effect of the anti-inflammatory compound mimosine

The plant amino acid mimosine has been demonstrated to arrest cell cycle progression in the late G1-phase, and inhibits [3H] thymidine incorporation in cultured fibroblasts. In this study, 10 mice were infected with Trichinella spiralis, a nematode parasite, and treated with the antiinflammatory compound L-mimosine to determine if any alteration in the chronic inflammatory state occurred by investigating the host's immunological response. Mimosine was used at 250 g/bolus for 25 days starting five days before the infection and continuing daily for 35 days then TNF, IFN-, IL-4, IL-6, and IL-10 were determined by ELISA method, after 0, 1, 7, 14, 21, 28, 35 days post-infection, in the serum of treated or untreated animals. When animals with T. spiralis were treated with L-mimosine, inhibition of TNF was observed within 21 days post-infection, compared with the controls (untreated mice). IFN was inhibited only up to the 21^st day, while IL-6 was inhibited up to the 7^th day post-infection and the inhibition of IL-4 was seen mainly at 21^st and 35^th day p.i. Mimosine-treated mice did not statistically affect the secretion of IL-10 (p > 0.05). In healthy animals, the production of cytokines were within the same limits compared with those of non-infected animals treated with L-mimosine. Our studies suggest that mimosine proved to be more effective in inhibiting TNF and IL-6, which are mainly produced by macrophages and less effective in inhibiting IL-4, which is produced by T-cells.     

Murine cytomegalovirus infection model in Balb/c mice. 3. Immunoglobulin production during infection.

In mice infected with a lethal dose of murine cytomegalovirus (MCMV) the serum immunoglobulin (Ig) levels and the Ig-bearing cells in the spleen dropped to barely detectable levels 2 days after infection. In mice with acute but non-lethal MCMV infection, the serum IgM was twice and the IgG 32 times that of the uninfected controls by Day 8 of infection; the numbers of spleen cells bearing IgM and the IgG subclasses (IgG1, IgG2a, IgG2b, IgG3) were also greatly increased. In the asymptomatically infected group, serum IgM remained unchanged but the IgG increased to 16 times that of uninfected controls by Day 11 of infection; the numbers of spleen cells bearing IgM and IgG subclasses were also increased, although to a lesser extent than in the acute, non-lethally infected mice. In the latter two groups, serum IgA and IgA-bearing cells in the spleen did not alter significantly. Complement-requiring neutralizing antibodies to MCMV were detected 8 days post infection.     

小于胎龄儿免疫球蛋白及补体C3、C4变化的探讨

目的：对小于胎龄儿（SGA）免疫球蛋白IgG、IgM、IgA及补体C3、C4变化的探讨。方法：取小于胎龄100，足月适于胎龄儿60例，生后第1、3、7天血清用免疫透射比浊法进行测定。结果：小于胎龄儿IgG、IgM、IgA、C3、C4明显低于足月适于胎龄儿，早产小于胎儿龄儿IgG、C3明显低于足月小于胎龄儿，小于胎龄儿第7天IgM有增加趋势，结论：小于胎龄儿免疫球蛋白IgG、IgM、IgA及补体C3、C4明显不足。     

Effect of the broad spectrum anthelmintic drug flubendazole upon Schistosoma mansoni experimentally infected mice

The effect of the broad spectrum anthelmintic drug flubendazole (methyl 5-(p-fluorobenzoyl)-2-benzimidazolecarbamate, CAS 31430-15-6), a mebendazole derivative with a molecular weight of 313.29, on Schistosoma mansoni infection in mice was evaluated. Moreover, the relationship between the posttreatment worm burden, hepatic granuloma volume, and serum immunoglobulin profile (immunoglobulin G and immunoglobulin M, IgG and IgM), was also investigated. Two main groups of Swiss albino mice infected with Schistosoma mansoni cercariae were used in the experiment. Group I consisted of infected untreated control mice. The mice of group II were submitted to treatment with flubendazole 100 mg/kg body weight as single oral dose at different time intervals: Group IIa received treatment 24 h before infection. Group IIb received treatment 4 h after infection. Group IIc received treatment 25 days after infection. Mice treated 25 days after infection, compared to those treated in other time intervals, revealed a significant reduction in the recovery of adult schistosomes after portal perfusion (79.5%), a lower immunoglobulin level (IgG and IgM), and the smallest granuloma mean diameter (220.0 +/- 10.3 microns). These data were less salient in mice treated 4 h after, and 24 h before infection.     

Lansoprazole increases serum IgG and IgM in H. pylori-infected patients

Proton-pump inhibitors have been reported to influence the human immune system, we therefore evaluated the effect of lansoprazole, a proton-pump inhibitor, on humoral immunity. Patients with gastric ulcer received lansoprazole 30 mg/day for 8 weeks, and serum immunoglobulins were evaluated before and upon completion of the treatment. There were 79 patients with gastric ulcer; 51 were H. pylori-infected and 28 were H. pylori-uninfected. Eighteen patients positive for H. pylori were receiving at least one non-steroidal anti-inflammatory drug, and 12 patients negative for H. pylori received one non-steroidal anti-inflammatory drug. H. pylori-infected patients showed significant increases in serum immunoglobulins G and M 8 weeks after the start of lansoprazole treatment (P<0.001 for IgG and P<0.01 for IgM), but uninfected patients did not. Even when H. pylori-infected patients receiving a non-steroidal anti-inflammatory drug or low-dose aspirin were analyzed separately, these increases were seen (P<0.001 for IgG and P<0.005 for IgM). Lansoprazole elevated serum levels of immunoglobulins G and M in gastric ulcer patients with H. pylori infection, particularly in those receiving non-steroidal anti-inflammatory drugs. Deducing from these observations, lansoprazole might alter the Th1 shift in the immune response induced by H. pylori infection.     

Serum immunoglobulin levels in monkeys treated with methylmercury

Observations on patients with Minamata disease and studies in mice and rabbits have demonstrated that MeHg decreases synthesis of antibodies toward pathogenetic and non-pathogenetic antigens. Our study was intended to verify this hypothesis by using monkeys as test animals. Four groups of Cynomologus monkeys were treated for 120 days with: 0, 0.4, 4.0 and 50 micrograms/kg b.w./day of MeHg. Every 15 days each monkey was examined and given a blood test to evaluate immunoglobulins G, M, A (IgG, IgM, IgA). A dose-dependent transient reduction of gamma globulin was observed in all test groups as compared to the control. This effect was clearly evident after 30 days of treatment and disappeared after 60 days. At the highest dose the immunoglobulin G was significantly decreased as compared to the control after 45 and 60 days of treatment. After 120 days, all the exposed groups showed significantly lower levels of immunoglobulin G. Immunoglobulin M was significantly lower in the groups given 4.0 and 50 micrograms/kg b.w./day compared to the control, after 45, 60 and 120 days.     

蒿甲醚对小鼠血清IgG及脾重的影响

青蒿素与青蒿酯钠的某些免疫作用已有报道。本文报道应用单向免疫扩散测定技术,测定了蒿甲醚对小鼠血清IgG含量的影响,还观察了蒿甲醚对脾脏重量的影响。动物用20～25g JCR纯种小鼠,按雌雄各半随机分组。蒿甲醚(桂林制药厂提供)与氯喹(重庆制药厂生产)均混悬于1％西黄蓍胶,供灌胃用。兔抗小鼠IgG抗血清及标准JCR小鼠血清抗原均为本实验室制备。     

Serum Immunoglobulin Levels in Monkeys Treated with Methylmercury

ABSTRACT

Observations on patients with Minamata disease and studies in mice and rabbits have demonstrated that MeHg decreases synthesis of antibodies toward pathogenetic and non-pathogenetic antigens. Our study was intended to verify this hypothesis by using monkeys as test animals. Four groups of Cynomologus monkeys were treated for 12 0 days with: 0, 0.4, 4.0 and 50 μg/kg b.w./day of MeHg. Every 15 days each monkey was examined and given a blood test to evaluate immunoglobulins G, M, A (IgG, IgM, IgA). A dose-dependent transient reduction of gamma globulin was observed in all test groups as compared to the control. This effect was clearly evident after 30 days of treatment and disappeared after 60 days.

At the highest dose the immunoglobulin G was significantly decreased as compared to the control after 45 and 60 days of treatment. After 120 days, all the exposed groups showed significantly lower levels of immunoglobulin G.

Immunoglobulin M was significantly lower in the groups given 4.0 and 50 μg/kg b.w./day compared to the control, after 45, 60 and 120 days.     

Stimulation of TH1 response by Helicobacter pylori neutrophil activating protein decreases the protective role of IgE and eosinophils in experimental trichinellosis

Th2 responses seem to play an important role in defence against Trichinella spiralis (Ts). The neutrophil Activating protein of Helicobacter pylori (HP-NAP), that induces IL-12, and IL-23 expression and shifts to Th1 allergen-specific Th2 cells in vitro was used as an anti-Th2 agent in BALB/c mice infected with T. spiralis. The muscle larvae (ML) burden was lower (p < 0.02) in untreated infected animals than those infected treated with HP-NAP. In both groups there was an inverse relationship between ML burden of each animal and total IgE level (controls: r -0.617, p = 0.0013 and HP-NAP-treated: r -0.678, p = 0.0001) or eosinophil count, evaluated in the same mouse on day 42 (r -0.390, p = 0.0592 and r -0.803, p = 0.0001, respectively). Inflammatory response around the nurse cell-parasite complex was significantly higher in HP-NAP-treated infected animals than in those untreated infected, on the contrary the number of eosinophils, counted around each complex was significantly lower in the first animal group. This study provides evidence of a powerful anti-Th2 activity in vivo by HP-NAP and for the partial protective effect of Th2 responses in T. spiralis infection.     

Response of ADA and its isoenzymes in mice infected by Trichinella spiralis and treated with mimosine

Infections caused by the nematode Trichinella spiralis (T. spiralis) are characterized by an inflammatory response in the host. The aim of this study was to identify and evaluate markers for monitoring mice infected with T. spiralis and treated with or without mimosine. The markers that have been used were total and differential white blood cell counts, subpopulations of lymphocytes, serum tADA and its isoenzymes ADA1 and ADA2 activity. The study included 3 groups of BALB/c mice. Group A consisted of 16 healthy mice, Group B of 16 mice infected with T. spiralis and treated with saline, and Group C of 16 mice infected with T. spiralis and treated with mimosine. The measurements were made once per week for the first six weeks continuously following the infection. According to our results, leukocytosis, lymphocytosis and increased percentages of adhesion molecules and CD4 lymphocytes were present in groups B and C one week post-infection. Total ADA activity as well as ADA1 and ADA2 was higher in groups B and C versus group A from the first week post-infection. The levels of tADA activity, ADA1 and ADA2 were higher in group B compared to those of group C and the difference was statistically significant (p<0.05) during the 4th week post-infection. The majority of tADA activity, essential for an efficient immune response, was derived from ADA1 which may have been produced by infected tissues. The elevated activities of tADA and ADA1 may be sensitive markers for infection of T. spiralis and for monitoring the course of the infection.     

槲皮素对降植烷诱导的红斑狼疮样小鼠模型的作用

目的：研究槲皮素对降植烷（pristane）诱导的红斑狼疮样小鼠模型的治疗作用。方法：18只BALB/c雌性小鼠随机分为3组,即正常对照组（NC组,n=6;实验首日生理盐水0.5 mL腹腔注射）;模型组（SLE组,n=6;实验首日降植烷0.5 mL腹腔注射）;脂质体槲皮素治疗组（LQ组,n=6;实验首日降植烷0.5 mL腹腔注射;第二日起槲皮素按体质量降植烷50 mg·kg^-1 剂量灌胃,隔日一次）。5个月治疗期结束后ELISA法测定各组小鼠血清自身抗体（ANA、抗ds-DNA和抗snRNP/Sm抗体）表达水平及采用免疫荧光法显示各组小鼠肾小球IgG蛋白沉积情况。结果：3组小鼠ANA、抗ds-DNA和抗snRNP/Sm抗体表达水平差异有统计学意义（F=51.791,39.745和30.411,P<0.01）。与SLE组相比,LQ组小鼠肾小球的IgG沉积明显减少,自身抗体表达水平显著降低,但LQ组自身抗体表达水平仍高于NC组（P<0.01）。结论：槲皮素能降低降植烷诱导的SLE样综合征小鼠模型自身抗体表达水平,并能减轻肾损伤程度,对SLE的治疗可能有一定作用。     

Host resistance to Trichinella spiralis infection in rats and mice: species-dependent effects of cyclophosphamide exposure.

Host resistance to Trichinella spiralis infection was compared in male rats (F344) and female mice (C57BL/6J) following various cyclophosphamide (CY) treatment schedules. Doses of CY given to mice were adjusted by body surface area to be comparable to rat doses. Adult parasite elimination was not affected by oral administration of 1.5, 3 or 6 mg CY/kg per day to rats or 1.05, 2.1 or 4.2 mg CY/kg per day to mice for 10 days. In rats, resistance was suppressed by a single oral dose of 80 mg/kg given the day prior to infection, but was not affected at 20 or 40 mg/kg. A single oral dose of 14, 28 or 56 mg CY/kg did not affect parasite expulsion in mice. Rats were also given four daily intraperitoneal (i.p.) injections of 20, 40 or 80 mg CY/kg per day and mice received 14, 28 or 56 mg CY/kg per day. Infected rats did not survive at the two higher dose levels and parasite expulsion was suppressed at 20 mg/kg per day; parasite expulsion was suppressed in mice by four i.p. injections of 56 mg CY/kg per day, but not by lower doses. In rats, doses of CY which suppressed adult parasite expulsion also severely suppressed the proliferative response of mesenteric lymph node cells (MLNC) to an extract of T. spiralis (TsE). However, significant suppression of TsE-driven blastogenesis occurred at a dose of CY which did not affect parasite expulsion, indicating that the proliferative response in rats was more sensitive to suppression than actual parasite elimination. In contrast, the proliferative response to the T cell mitogen concanavalin A was elevated in the MLNC of CY-exposed rats. This was determined to be related to the interval between CY dosing and the day of assay rather than to an effect of infection with T. spiralis. Mouse MLNC proliferative responses to TsE were not suppressed by CY treatment, even at levels of CY which suppressed adult parasite expulsion. Mice differed from rats in that CY exposure did not affect the proliferative response to concanavalin A in infected animals. The species-dependent differences observed in these studies may have been secondary to the greater sensitivity of rats to CY. Nonetheless, these results highlight the potential for species-specific responses to chemical exposure and underscore the need for additional comparative studies of host resistance in rats and mice.     

Influence of chronic lead ingestion on IgG subclass expression of the immune response to bovine serum albumin

Rats were given free access to drinking water containing 2% lead acetate for 30 days prior to intraperitoneal inoculation with 100 mcg of bovine serum albumin (BSA) in Freund's complete adjuvant. Three weeks later, the animals were boosted with the antigen in Freund's incomplete adjuvant. After an additional three weeks, the animals were bled and the sera assayed for total IgG by radial immunodiffusion and for specific IgM, IgG and IgG subclasses by the enzyme-linked immunosorbent assay (ELISA). BSA-inoculated rats exhibited similar levels of total IgG regardless of exposure to lead, but showed significant increases in IgG compared to nonimmunized controls. However, levels of IgG specific for BSA were significantly lower in the lead exposed group. Analysis of the IgG subclasses specific for BSA revealed that BSA-inoculated rats which were not exposed to lead had greater titers of IgG2b and IgG2c as compared to the lead exposed group. Chronic lead ingestion appears to diminish the overall IgG response to BSA and may alter the normal IgG subclass expression.     

Correlation between infection intensity, serum immunoglobulin profile, cellular immunity and the efficacy of treatment with praziquantel in murine schistosomiasis mansoni

This study was conducted to evaluate the efficacy of praziquantel (CAS 55268-74-1, EMBAY 8440, Biltricide) in different grades of Schistosoma mansoni infection. Moreover, the relationship between the post treatment worm burden, hepatic granuloma volume, and serum immunoglobin profile was also investigated. Four groups of Swiss albino mice infected with Schistosoma mansoni cercariae were used: Highly infected untreated control mice (infected with 120 Schistosoma mansoni cercariae) and their corresponding praziquantel treated group. Lightly infected untreated control mice (infected with 60 Schistosoma mansoni cercariae) and their corresponding praziquantel treated group. Praziquantel was given seven weeks post infection in a dose of 500 mg/kg body weight for two consecutive days. Animals were sacrificed two weeks post treatment. Praziquantel achieved better cure rates in mice with heavy infection than in less intensely infected animals. The drug reduced the hepatic granuloma in animals with light intensity infection. This reduction was more accentuated in highly infected animals. The serum immunoglobulin profile (immunoglobulin G and immunoglobulin M) showed a higher level in highly infected treated mice (1.2 +/- 0.6 optical density unit and 1.1 +/- 0.5 optical density unit, respectively) and was reduced in animals with low intensity infection (1.18 +/- 0.6 optical density unit and 0.7 +/- 0.6 optical density unit, respectively). This study may be of value in tropical regions, where schistosomiasis with low worm burden is a common occurrence.     

Protective effects of a kampo medicine,Hochu-ekki-to (TJ-41) on lethal malarial infection with <Emphasis Type="Italic">Plasmodium chabaudi</Emphasis> AS in A/J mice

Effects of Hochu-ekki-to (TJ-41) on the course of lethal rodent malarial infection with Plasmodium chabaudi AS were examined in male A/J mice. We examined the mortality, parasitemia and serum cytokines such as IL-12, IFN-γ and IL-4 in the infected and TJ-41-treated/infected mice. There was a significant difference in mortality between infected and treated/infected mice. A high mortality was observed in male mice after infection with P. chabaudi AS. In mice treated with TJ-41, control of the primary infection was achieved, and significantly lower mortality was observed. All surviving males in the treated/infected group showed somewhat smaller peak parasitemias than those in infected controls. Mice in the infected and treated/infected groups displayed significantly elevated serum IL-12 levels on day 4 of infection when compared with the levels from the uninfected animals. Mice in the infected and treated/infected groups displayed significantly elevated serum IFN-γ levels when compared with the levels from the uninfected animals. Furthermore, a significantly higher IFN-γ level was seen in the treated/infected group than that in the infected group on day 4 of infection. The present results suggest that an early production of IFN-γ in the TJ-41-treated/infected mice is associated with a decrease of parasitemia, being responsible for the survival of mice.     

新型冠状病毒B.1.617.2变异株感染儿童血清IgM、IgG特点分析及思考

目的:分析新型冠状病毒B.1.617.2变异株感染儿童的血清免疫球蛋白（Ig）M、IgG特点,为大疫情时代下疫情防控提供参考。方法:研究组为2021年5月26日至2021年6月11日广州医科大学附属市八医院确诊的28例（年龄2～17岁）新型冠状病毒B.1.617.2变异株感染患儿。对照组为同期变异株感染成人患者125例...     

Immunotoxicology studies on octoxynol-9 and nonoxynol-9 in mice

In a double-blind study, mice were injected intraperitoneally with 0.2 ml 0.2% octoxynol-9 (O-9), 0.2 ml 0.2% nonoxynol-9 (N-9), or 0.2 ml saline (control) daily for 24 days. Another control group received no treatment. All mice were immunized twice with sheep red blood cells (SRBC) and bled by caudal incision. Mice receiving N-9 lost weight (P less than 0.02), had smaller livers (P less than 0.05), and showed enlarged spleens (P less than 0.05). The N-9-treated mice did not differ from either control group in the primary or secondary anti-SRBC responses, leukocyte (WBC) counts, or in the sizes of the kidneys, hearts, lungs, or thymuses. Mice receiving O-9 showed no significant differences from either control group in any of these tests. Serum immunoglobulin M (IgM) and immunoglobulin G (IgG) levels were similar in mice treated with O-9, N-9, or saline. All 3 groups had higher levels of both classes of immunoglobulins on day 16 than did untreated controls. This study shows that O-9, given to mice in doses 3 times that used by humans, is nontoxic, whereas the same dose of N-9 has minor deleterious effects.     

Study of acute chagasic mice under immunosuppressive therapy by cyclosporin A : modulation and confocal analysis of inflammatory reaction

The in vivo effects of cyclosporin A (CsA) on Trypanosoma cruzi infection were examined using different schedules of the drug in mice infected with the Y strain. Parasitaemia at day 8 after infection among CsA-treated animals was usually higher than control infected non-treated mice. On the other hand, mortality analysis showed that animals CsA-treated either with 200 mg/kg 2 days before infection or with therapeutic doses (10 mg/kg every other day) showed almost the same mean time of death (35.8 and 38.2 days, respectively). In these groups mice died 50% less than control infected non-treated ones. The mean time of death in the animals treated with 200 mg/kg 5 days after infection and in infected non-treated control mice were respectively 29.0 and 22.6 days. The kinetics analysis of the leukocyte population of animals treated with a single dose of 200 mg/kg of CsA before or after infection did not show the alternate pattern of leukopenia/leukocytosis observed in control groups of infected mice but differential cell counts indicated a modulatory action upon circulating leukocytes of therapeutic doses of CsA. The animals treated with any of the CsA schedules showed a moderate to intense diffuse inflammatory reaction exhibiting mainly mononuclear cells in the heart. Immunofluorescence analysis by confocal microscopy revealed that macrophages are a major component of the inflammatory infiltrate in all groups of CsA-treated mice and also in the control group.