Increased levels of IL-10, IL-12, and IFN- in patients with visceral leishmaniasis.

Visceral leishmaniasis remains a serious public health problem in developing countries. Cytokines have a crucial role in the pathogenesis of this disease. We evaluated plasma levels of IL-10, IL-12 and IFN- in 32 patients with active visceral lieshmaniasis, in 29 siblings of the patients and in 23 normal individuals in an endemic area to look for correlations between the clinical outcome of infection and the plasma cytokine levels. An analysis was made with a skin test and a quantitative sandwich enzyme immunoassay. Data were analyzed with the Mann Whitney test and the Kruskal Wallis test. The cytokine levels were significantly higher in the patients than in the control groups. We concluded that normalization of the plasma level of IFN- can serve as a reliable parameter for considering the patient as cured.

The effect of severe zinc deficiency and zinc supplement on spatial learning and memory.

Zinc deficiency during pregnancy and during lactation has been shown to impair cognitive function and motor activity in offspring rats. In the present study, the effect of zinc deficiency and zinc supplement on spatial learning and memory in Morris Water Maze (MWM) and motor activity in open field were investigated. Pregnant rats after mating were divided to three groups. Control group fed a standard diet and a zinc deficient (ZnD) group fed a diet deficient in zinc (0.5-1.5 ppm) and a zinc supplement (ZnS) group fed a standard diet and enhanced zinc in the drinking water (10 ppm). All the diets were exposed during the last trisemester of pregnancy and during lactation. Rat's offspring in these groups were tested for spatial learning and memory in MWM at post natal day (PND) 56 and were tested for motor activity in open field at PND 66.The Escape Latency (EL) and Traveled Distance (TD) in the ZnD group were increased but Percentage of Time Spent in the target quadrant (PTS) was decreased compared to the control group. In addition, these were no significant differences in EL and TD, but PTS had significant increase in ZnS compared to the control group. In the open field, Total Distance Moved (TDM) and Time of Motor Activity (TMA) for the ZnD were decreased compared to the control group, but there were no significant differences in TDM and TMA between control and ZnS groups. These findings suggest that zinc deficiency during the last trimester of pregnancy and during lactation impaired spatial learning and memory in their offsprings and has also negative effect on motor activity. In addition, ZnS has a significant effect on spatial learning and memory but no effect on motor activity in their offsprings.

Increased levels of IL-10, IL-12, and IFN- in patients with visceral leishmaniasis

Visceral leishmaniasis remains a serious public health problem in developing countries. Cytokines have a crucial role in the pathogenesis of this disease. We evaluated plasma levels of IL-10, IL-12 and IFN- in 32 patients with active visceral lieshmaniasis, in 29 siblings of the patients and in 23 normal individuals in an endemic area to look for correlations between the clinical outcome of infection and the plasma cytokine levels. An analysis was made with a skin test and a quantitative sandwich enzyme immunoassay. Data were analyzed with the Mann Whitney test and the Kruskal Wallis test. The cytokine levels were significantly higher in the patients than in the control groups. We concluded that normalization of the plasma level of IFN- can serve as a reliable parameter for considering the patient as cured.

Systemic and mucosal immunity is elicited after both intramuscular and intravaginal delivery of human immunodeficiency virus type 1 DNA plasmid vaccines to pregnant chimpanzees.

DNA vaccines encoding human immunodeficiency virus type 1 (HIV-1) env/rev and gag/pol were delivered intravaginally (IVAG) and intramuscularly (IM) to 2 pregnant chimpanzees. Vaccination was well tolerated and each chimpanzee developed antibodies (up to 1 year later) to both vaccines. Placental transfer of anti-Env and anti-Gag IgG was demonstrated in both maternal/infant pairs. Specific IgG was also demonstrated in saliva, vaginal, and rectal washes after IVAG immunization. Predominantly anti-HIV-1 IgA was detected in the milk of both mothers after both IM and IVAG immunization. Cellular responses included Gag-specific proliferation of lymphocytes and cytotoxic T lymphocytes against both antigens. These data suggest a strategy for induction of mucosal and systemic responses after both IM and IVAG delivery of DNA vaccines in a primate model and could ultimately be useful in lowering maternal-to-fetal transmission of HIV-1, perinatally and through breastfeeding.

Safety and immunogenicity of HIV-1 DNA constructs in chimpanzees.

A global effort to control the HIV epidemic is likely to rely heavily on immunization strategies. As our closest genetic relative, the chimpanzee provides the most important model for preclinical safety and immunogenicity studies. We have immunized adult, pregnant and infant chimpanzees with our plasmid vaccines. We have found these vaccines to be safe and well tolerated in all of these groups. The same vaccines have induced both humoral and cellular immunity in each instance.

Safety and immunogenicity of intramuscular and intravaginal delivery of HIV-1 DNA constructs to infant chimpanzees.

Any global strategy for controlling the human immunodeficiency virus (HIV) epidemic is likely to rely heavily on immunization of infants and children. Given the well-documented differences in children's responses to traditional vaccines, we initiated this study to extend our findings on DNA vaccination of adult chimpanzees to immunologically immature infant chimpanzees. Our findings were consistent with our previous work in adults as we observed that the DNA vaccines used here were both well tolerated and immunogenic within weeks of the initial vaccination.

Lymphocyte and neutrophil dysfunction associated with hepatitis B virus and hepatitis non-A, non-B virus infection in the chimpanzee.

Chimpanzees were examined for the effect of viral hepatitis infections on specific and nonspecific immune response mechanisms. The data suggest that infection with either hepatitis B virus or hepatitis non-A, non-B virus may result in suppression of cellular immune response components. Mitogen-induced lymphocyte proliferation was lower in virus-infected chimpanzees than in naive animals. Neutrophils from virus infected animals exhibited decreased or altered chemiluminescence kinetics.

Polymorphonuclear leukocyte function in HIV-1-infected chimpanzees.

The chemiluminescent characteristics of enriched populations of neutrophils from control and HIV-infected chimpanzees were assessed. Neutrophils from HIV-infected chimpanzees were suppressed in their ability to generate a normal response to particulate and soluble stimuli when compared to normal and hepatitis non-A, non B-infected controls. Particulate (latex beads) stimulation of neutrophils resulted in an aberrant response when contrasted with controls. Normal control responses were characteristically biphasic while the response from hepatitis NANB HIV-infected chimpanzees was not biphasic. Neutrophils challenged with a soluble (phorbol ester) stimulant also demonstrated a suppressed response. These data suggest that HIV infection has an additive suppressive effect on neutrophil function in chimpanzees previously infected with hepatitis NANB. The suppression of chimpanzee neutrophil function following HIV infection is similar to that seen in other non-primate viral and retroviral infections.