Basic and biomedical product-oriented research - the National Institute of Immunology

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Intrauterine Growth Restriction: Cytokine Profiles of Trophoblast Antigen-Stimulated Maternal Lymphocytes

Intrauterine growth restriction (IUGR) is an important perinatal syndrome that poses several serious short- and long-term effects. We studied cytokine production by maternal peripheral blood lymphocytes stimulated by trophoblast antigens. 36 women with a diagnosis of IUGR and 22 healthy women with normal fetal growth were inducted. Peripheral blood mononuclear cells were stimulated with trophoblast antigens and levels of the proinflammatory cytokines IL-6, IL-8, IL-12, IL-23, IFNγ, and TNFα and the anti-inflammatory cytokines IL-4, IL-10, and IL-13 were measured in culture supernatants by ELISA. IL-8 was produced at higher levels by blood cells of the IUGR group than normal pregnant women, while IL-13 was produced at lower levels. IL-8, IFNγ, and TNFα were higher in IUGR with placental insufficiency than in normal pregnancy. IL-12 levels were higher and IL-10 levels were lower in IUGR with placental insufficiency than in IUGR without placental insufficiency. We suggest that a stronger pro-inflammatory bias exists in IUGR as compared to normal pregnancy and in IUGR with placental insufficiency when compared to IUGR without placental insufficiency. Several ratios of proinflammatory to anti-inflammatory cytokines also support the existence of an inflammatory bias in IUGR

Does 3-Day Course of Oral Amoxycillin Benefit Children of Non-Severe Pneumonia with Wheeze: A Multicentric Randomised Controlled Trial

WHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph.This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2-59 months of age, who received either oral amoxycillin (31-54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4.We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92).Treating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin.ClinicalTrials.gov NCT00407394

SyD: A Middleware Testbed for Collaborative Applications over Small Heterogeneous Devices and Data Stores

Abstract. Currently, it is possible to develop a collaborative application running on a collection of heterogeneous, possibly mobile, devices, each potentially hosting data stores, using existing middleware technologies such as JXTA, BREW, compact.NET and J2ME. However, they require too many ad-hoc techniques as well as cumbersome and time-consuming programming. Our System on Mobile Devices (SyD) middleware, on the other hand, has a modular architecture that makes such application de-velopment very systematic and streamlined. The architecture supports transactions over mobile data stores, with a range of remote group invo-cation options and embedded interdependencies among such data store objects. The architecture further provides a persistent uniform object view, group transaction with Quality of Service (QoS) speci¯cations, and XML vocabulary for inter-device communication. This paper presents the basic SyD concepts, introduces the architecture and the design of the SyD middleware and its components. We also provide guidelines fo

Manipulation of Cytokine Production Profiles as a Therapeutic Approach for Immunologic Pregnancy Loss

229-236Pregnancy is not as successful as one might think; it can be compromised by several complications such as recurrent spontaneous miscarriage, pre-term delivery, pre-eclampsia etc. Much attention has been paid to the possibility of the maternal immune system mediating deleterious effects on pregnancy. Research conducted during the last two decades has shed much light on cell-mediated immunologic effectors that might underlie these pregnancy complications. Of particular interest are the effects that pro-inflammatory and anti-inflammatory cytokines have on the foetus and placenta, and thus on the success and failure of pregnancy. This review presents evidences that certain cytokine profiles are associated with recurrent miscarriage and pre-term delivery and discusses possible pathways of effector function of cytokines in pregnancy loss and the redirection of cytokine profiles from one that is antagonistic to pregnancy towards one that is conducive to the success of pregnancy. Among the promising agents for the modulation of the Th1/Th2 balance are progestogens like progesterone and dydrogesterone; this review also discusses recent evidence that progestogens are capable of modulating cytokine production patterns in pregnancy loss

Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy

Progesterone is well known for its numerous endocrinologic roles in pregnancy but is also endowed with fascinating immunomodulatory capabilities. It can downregulate the induction of inflammatory reactions, the activation of immune cells and the production of cytokines, which are critical mediators of immune responses. These features appear to be critical to the success of pregnancy, given the ability of maternal immune reactivity to interfere with pregnancy and to contribute to several pregnancy complications. This review summarizes the contribution of maternal immune effectors in general, and cytokines in particular, to pregnancy complications such as recurrent miscarriage, pre-eclampsia and preterm labor; it describes the promise offered by supplementation with progesterone and the oral progestogen dydrogesterone, as well as the progesterone-induced blocking factor in the prevention and/or treatment of these serious complications

Anti-fertility vaccines

Vaccines are under development for the control of fertility in males and females. This review discusses developments in anti-fertility vaccines at the National Institute of Immunology, New Delhi, India. A single injection procedure for the sterilization or castration of male animals depending on the site at which the injection is given, has passed through field testing and is expected to be on the market in the near future. Vaccines inducing antibodies against the human chorionic gonadotropin have gone through phase I trials with satisfactory results. A vaccine producing a consistently bioeffective antibody response against gonadotropin-releasing hormone is ready for phase I/II clinical trials in patients of carcinoma of prostate after due experimenation in animals and toxicology studies. Research to identify sperm antigens for incorporation into second generation vaccines is in progress

Vaccines against fertility

The first evidence for the efficacy of a birth control vaccine in humans is now available from the Phase II trials on the human chorionic gonadotrophin vaccine in India. Several sperm antigens have been identified as potential contraceptive immunogens and zona pellucida antigens have been reported that reversibly control fertility

Influence of the genetic background and carrier protein on the antibody response to GnRH

A vaccine against the gonadotropin releasing hormone (GnRH) is being developed as an immunological method for the treatment of prostatic enlargement. The work described here was aimed at investigating the influence of the genetic background on immune responses to GnRH conjugated to diphtheria toxoid (DT). Mice of different strains were injected with the conjugate and the antibody levels against GnRH and DT quantitated in order to examine the effect of genetic background on immune responses to the hapten and the carrier. All immunized animals produced antibodies to DT. Anti-GnRH antibodies were generated by all strains of mice except 129. The low anti-GnRH response in the 129 strain mice did not appear to be MHC-linked, as C57BL/6 mice, which bear the same MHC haplotype as 129 mice, were able to generate a strong anti-GnRH response. The non-responsiveness to the hapten (GnRH) in 129 strain mice was overcome by the use of an 'alternate carrier' approach