Aqueous extracts from dietary supplements influence the production of inflammatory cytokines in immortalized and primary T lymphocytes.

BACKGROUND: Congaplex and Immuplex are dietary supplements that have been traditionally used to support immune system function. The purpose of these experiments was to determine whether Congaplex and Immuplex affect immune function using primary and immortalized T lymphocytes. METHODS: Immortalized CEM and Jurkat T lymphocytes and primary peripheral mononuclear blood cells (PBMCs) were treated with the aqueous extracts from Congaplex and Immuplex to determine the effects of these products on cytokine production in activated T lymphocytes. RESULTS: Congaplex enhanced phytohemagglutinin/phorbol 12-myristate 13-acetate (PHA/PMA) stimulation of both CEM and Jurkat cells as measured by the production of cytokines, while Immuplex suppressed PHA/PMA-induced production of cytokines, with the exception of interleukin (IL)-8 which was enhanced by Immuplex. In vitro treatment of PBMCs from 10 healthy donors with Congaplex or Immuplex decreased PHA-stimulated production of interferon (IFN)-gamma but increased the production of IL-13. CONCLUSIONS: While the effects of Congaplex and Immuplex differed in these two models, these data demonstrate that the aqueous extracts from these two dietary supplements can affect the inflammatory response of T lymphocytes.

Effect of calf thymus extract and zinc supplementation on the cellular response of mice exposed to restraint stress.

The studies were carried out on Balb/c mice exposed to restraint stress twice for 12 h at 24 h intervals. Prior to stress exposure, the mice were treated with calf thymus extract (TFX - Jelfa) i.p. at a dose of 10 mg/kg, ten times at 24 h intervals. TFX was used per se or with zinc ions interaction, by adding zinc ions (as sulfate salt) to drinking water at a dose of 72 microg/mouse per day. The results obtained show that restraint stress dramatically decreased the total number of thymocytes and splenocytes which is also accompanied by decreasing weight ratio of the thymus and spleen. The decreasing number of thymic and spleen cells corresponded to a diminishing percentage of immature, double-positive CD4+CD8+ thymocytes, mature single-positive CD4+ thymic cells and CD4+, CD8+ and CD19+ splenocytes. Changes in the number of thymic cells affect their activity, which is expressed as a decreased proliferative response of thymocytes stimulated in vitro with concanavalin A (Con A) and phytohaemagglutinin (PHA). Besides, exposure to the restraint stress decreased interleukin-1 (IL-1) production by murine intraperitoneal macrophages stimulated in vitro with lipopolisacharide (LPS) from E. coli. Previous treatment with TFX counteracted restraint stress-induced immunosuppression, which is expressed as partial normalisation of the total number of thymic and spleen cells, accelerated regeneration of these two lymphatic organs, shortned suppressive action of restraint stress on the percentage of immature CD4+CD8+ thymocytes and CD4+ splenocytes and in total normalisation of the CD4+ thymocytes and CD8+ splenocytes. TFX administered prior to restraint stress not only counteracted the suppresive effects of stress on the proliferative activity of thymic cells stimulated in vitro with Con A and PHA, but also augmented the proliferative response of these cells to two mitogens. The immunorestorative effect of TFX was augmented by zinc supplementation.

The influence of nonspecific immunostimulation of pregnant sows on the immunological value of colostrum.

The purpose of this experiment was to estimate the influence of nonspecific immunostimulation of pregnant sows on the immunological value of colostrum. The studies were done in the fall-winter season on 20 pregnant sows (Polish Landrace) divided into four groups, five animals each. The sows were clinically healthy and unvaccinated. Group I received isoprinosine, group II (TFX), group III (HMB), and group IV served a control. The immunostimulants were applicated 4-6 weeks before the expected date of delivery. The following parameters were determined in colostrum taken from sows after completed delivery: specific gravidity; total proteins, lysozyme activity, IgG level. It was found that the nonspecific immunostimulation of pregnant sows increased in colostrum the level of IgG, total protein content and lysozyme activity.

[The effect of the preparation Wobe-Mugos E on the functional and biochemical status of the kidneys in the polyuric stage of sublimate-induced nephropathy]. / Vplyv preparatu Wobe-Mugos E na funktsional'nyi ta biokhimichnyi stan nyrok u poliurychnu stadiiu sulemovoï nefropatiï.

The protective effect of Wobe-Mugos appliance on the kidney function and biochemical state in polyuric stage of sublimate nephropathia at the moment of tubulointerstitial component formation was revealed in experiments on 40 white male rats. It appeared in the increase of hydrogenous ion excretion, titred acids, renal tissue fibrinolytic and proteolytic activity. The succinatdehydrogenase activation in renal cortex matter pointed out on the improvement of energy balance.

Modulation of mouse brain cortex adrenoceptor in old mice by supplementation of zinc and thymomodulin.

BACKGROUND: Previous experiments have shown that the age-related decrease of mouse brain cortex adrenoceptor density can be recovered by grafting a neonatal thymus into old recipients. The question arises whether similar results can also be obtained in the presence of a single thymic factor such as thymomodulin (TMD). It is worth noting that the activity of some thymic factors is strictly zinc (Zn) dependent and that their age-related decreased production is recovered in old mice supplemented with Zn. OBJECTIVE: The above-mentioned evidences prompted us to verify whether Zn and TMD, either alone or combined, are able to induce some corrective effects on age-dependent alterations of adrenoceptor characteristics of the mouse brain cortex. METHODS: Thus, we performed experiments on four groups of Balb/c mice treated with saline, Zn, TMD, or both Zn and TMD. Treatments started when animals were 18 months old and ran for 6 months. The alpha(1)- and beta-Adrenoceptor characteristics were assayed by steady state binding analysis using labelled prazosine and iodocyanopindolol, respectively. Data were analyzed using one-way analysis of variance, followed, when appropriate, by multiple-comparison analysis. RESULTS: Results show an increase of beta-adrenoceptor density and a decrease of alpha(1)-adrenoceptor density in both Zn- and Zn+TMD-treated animals when compared to saline-treated controls, while receptor affinities did not change significantly. CONCLUSIONS: The lack of action of TMD suggests that this type of treatment cannot mimic the effects of grafting the whole gland; it cannot be excluded that different time-dose schedule could be more effective. Zn treatment, on the other hand, does modulate adrenoceptors; however, it shows a corrective action on the age-related decreased density of beta-adrenoceptors, but further decreases that of alpha(1)-adrenoceptors. This differential action could be due to their differential physiological role.

Effects of non-specific immunostimulants (echinacin, isoprinosine and thymus factors) on the infection and antigen expression in herpesvirus-6 exposed human lymphoid cells.

Non-specific immunostimulants such as plant extracts and natural and synthetic thymic preparations are widely used for enhancing the reactivity of the human defence system in chronic infections, immunodeficiency, autoimmunity and neoplastic diseases. Considering the high prevalence of latent infections by Lymphotropic herpesviruses and their frequent spontaneous reactivation, one wonders whether the stimulation of lymphoid cells by such immunostimulants may further support virus reactivation. We have performed tissue culture experiments using the well defined infectious system of human herpesvirus-6 (HHV-6) and the immature T cell HSB2 to test the effects of echinacin, isoprinosine and thymus factors on the frequency and extent of virus antigen expression in infected cells. The results show that various viral antigens related to virus replication and to the synthesis of structural components appear earlier in cells stimulated with such substances as echinacin, timunox and TP-1, but not following the stimulation with isoprinosine. Similarly, virus genome containing cells as determined by in situ hybridization techniques increased after stimulation with thymic preparations (thymostimulin and thymopentin), but not with echinacin and isoprinosine. The data suggest that the synthesis of proteins or DNA of lymphotropic viruses may be transiently enhanced when lymphoid cells are stimulated by certain non-specific immunostimulants. There was no evidence, however, of increased virus replication. Since the data presented here are rather preliminary results from tissue culture studies, the use of such substances in patients should include a critical monitoring of the activity of lymphotropic viruses to exclude untoward effects through persistent viral activity and/or autoimmune dysregulations (e.g. secondary to selective expression of viral antigens). More detailed studies are needed to this effect including long-term controls in patients treated by these substances.

[Biorhythms of the lymphoid system and possibilities of immunomodulating chronotherapy]. / Bioritmy limfoidnoi sistemy i vozmozhnosti immunomoduliruiushchei khronoterapii.

The paper provides the authors' own data and the data available in the literature concerning diurnal rhythms of immunological parameters in the development of experimental immunopathological conditions. Desynchronizing these rhythms, a change in the light regime is shown to accelerate the time course of the development of an autoimmune process in mice. The potentialities of chronotherapy of experimental immunodeficiencies with thymic preparations have been studied. It is emphasized that chronobiological studies are particularly essential in solving the biomedical problems of the Far North with its extreme conditions and a great deal of desynchronizing factors.

Immunorestorative effect of thymostimulin on surgery immunodepression: experimental model.

The purpose of the present study is to ascertain the immunorestorative effect of two different drugs on immunodepression induced by small bowel surgical resection in an experimental model. The potential immunorestorative effect has been measured by the ability of the drug to avoid the delay of skin allograft rejection induced by surgery and the inhibition of CD4/CD8 index changes induced by surgery in spleen tissue. 120 Wistar-Furth rats (age 12-16 weeks) anesthetized with a single intramuscular dose of ketamine (25 mg), diazepine (4 mg) and atropine (0.1 mg) were allotted to two main groups. One group received a skin graft (SG) from Fisher 344 rats and was treated with placebo, Inmunoferón (AM-3 polypeptidic drug) or TP-1 (thymostimulin) before the experiment (groups I, II, III) or treated with placebo, Inmunoferón or TP-1 before the experiment and underwent enterectomy and anastomosis (groups IV, V, VI). On the 2nd, 5th and 8th postoperative days, biopsies of the SG were taken and the signs of rejection were microscopically studied and evaluated by a pathologist as zero, incipient, moderate or massive. The other group was treated similarly, but the animals did not receive a SG and were splenectomized 5 days later. CD4 and CD8 lymphocyte subpopulations were identified by means of immunoperoxidase technique and monoclonal antibodies. Thymostimulin is able to stimulate the presence of SG rejection signs on the 2nd postoperative day in nonenterectomized animals and on the 8th postoperative day in nonenterectomized animals and on the 8th postoperative day in enterectomized rats and is able to avoid the decrease of the CD4/CD8 index in spleen tissue after surgical immunodepression.(ABSTRACT TRUNCATED AT 250 WORDS)

[Action of various immunomodulators on hematopoiesis]. / Deistvie nekotorykh immunomoduliatorov na gemopoéz.

In experiment on Wistar rats the effect of immunomodulators on hemopoiesis in cases of iron deficiency anemia under conditions of ferrotherapy was studied. Tactivine was shown to induce activation of granulocytopoiesis in combination with erythropoiesis inhibition. Sodium nucleinate led to some stimulation of erythrone and weak inhibition of leukopoiesis. Levamisole showed inhibitory effect on hemopoietic tissue. The data obtained are to be taken into account in immunocorrection of hemopoiesis disorders.

[Distribution in mice of 125I-monoclonal antibodies to T-lymphocyte antigen Ly 2.1 under the influence of immunomodulators]. / Raspredelenie u myshei 125I monoklonal'nykh antitel k antigenu Ly 2.1 T-limfotsitov pod vliianiem immunomoduliatorov.

A study was made of the distribution of 125I (a chloramine method of labeling) monoclonal antibodies to the surface antigen Ly 2.1 of T-lymphocytes during action of immunomodulators (tactivin, hydrocortisone, tactivin administered after hydrocortisone) on ACR mice. These antibodies were shown to retain antigen binding capacity, permitting monitoring of the redistribution of the antigen in the body exposed to immunomodulators.

[Effect of taktivin on diuresis and tubular cardiotrast secretion in the kidney]. / Vliianie taktivina na mocheotdelenie i kanal'tsevuiu sekretsiiu kardiotrasta v pochke.

The effect of a new immunomodulator taktivin (7-20 micrograms/kg subcutaneously, for 6 days) on the diuresis and tubular transport of cardiotrast (diodrast) was studied on rats. taktivin was shown to increase the tubular transport of the xenobiotic without significant changes in glomerular filtration and renal excretion of water, sodium, potassium, uric acid and creatinine. Possible mechanism of taktivin's action on the tubular transport of xenobiotics is discussed.

[Phenotypic correction of the immune response by L-tyrosine in mice reacting oppositely to sheep erythrocytes]. / Fenotipicheskaia korrektsiia immunnogo otveta L-tirozinom u myshei, oppozitno reagiruiushchikh na éritrotsity barana.

The possibility of transversion of low-reacting mice into high-reacting ones evaluated by the application of the natural immunostimulators. L-tyrosine and thymic polypeptides (taktivin) were compared by their ability for the phenotypical correction of the immune response of the oppositely reacting mice. It was established that under the application of L-tyrosine to oppositely reacting mice the phenotypical correction of the immune response is possible. The dramatic increase in AFC and the AFC-SI secreting IgM is observed in the mice, low-reacting to SRBC in comparison with the high-reacting lines.

Update and future perspectives of a thymic biological response modifier (Thymomodulin).

Thymomodulin (Ellem Industria Farmaceutica spa, Milan, Italy) is a calf thymus acid lysate with immunomodulating activities. It is composed of several peptides with a molecular weight range of 1-10kD. Extensive studies in animal systems showed that Thymomodulin exhibited no, or very little toxicity even when used at high doses. Studies done in vitro and in vivo demonstrated that Thymomodulin is a biologically active compound which regulates the maturation of human and murine pre T lymphocytes, as well as modulate the functions of apparently mature human and animal B and T lymphocytes. It was observed that Thymomodulin can promote myelopoiesis as demonstrated by an increase of granulocyte-macrophage colonies in agar. Although additional studies to examine its target cell lineage are required, it appears that Thymomodulin exhibits specificity toward T cells. Therefore, enhancement of other cell lineage functions by Thymomodulin may be indirect, and mainly due to its effect on T cells. Of major importance is to note that Thymomodulin is prepared in a manner which allows it to maintain its biological activity when administered orally.

[Receptors for lactoferrin on human thymic lymphocytes. The stimulation of expression as affected by adenosine, theophylline and a supernatant of thymic lymphocytes]. / Retseptory dlia laktoferrina na limfotsitakh timusa cheloveka. Stimuliatsiia ékspresii pri deistvii adenozina, teofillina i dekantata limfotsitov timusa.

It was established by indirect immunofluorescence with the use of antibodies to human lactoferrin that thymic lymphocytes bear lactoferrin receptors in the point structures on the cell surface. The ability of thymic lymphocytes to express lactoferrin receptors depends on the cAMP concentration in the cell, inasmuch the treatment of lymphocytes with adenosine and theophylline increases the number of cells bearing lactoferrin receptors. Supernatant of thymic lymphocytes is also capable of stimulating expression of lactoferrin receptors. It is assumed that these treatments can be used for increasing the number of lymphocytes with lactoferrin receptors with the purpose of separation and study of the function of this subpopulation in health and in different pathological conditions.

[The influence of low-molecular extracts from heterologous thymus, epiphysis and hypothalamus on the immune response in mice]. / Vliianie nizkomolekuliarnykh ékstraktov iz geterologichnykh timusa, épifiza i gipotalamusa na immunyi otvet u myshei

Extracts from bovine tissue were prepared by the acetic acid treatement and purified by gel filtration. All the preparations were injected into CBA mice for 10 days. Extracts from the thymus and the epiphysis proved to increase the number of antibody-forming cells generated in the spleen and the level of serum hemagglutinins in response to the immunization with sheep red cells. As to the hypothalamic extract, it depressed the immune response.