Macrophage infiltration of the kidney is a prominent feature associated with the severity of renal injury and progressive renal failure. To determine the influence of macrophages in renal disease models in the absence of endogenous T and B cells, we performed adoptive transfer of macrophages into severe combined immunodeficient (SCID) mice. In this study, macrophages were isolated from the spleens of BALB/c mice and stimulated with lipopolysaccharide to induce classically activated M1 macrophages or with interleukin-4 (IL-4) and IL-13 to induce alternatively activated M2 macrophages. These macrophages were then infused into SCID mice with adriamycin nephropathy; an in vivo model of chronic inflammatory renal disease analogous to human focal segmental glomerulosclerosis. Mice infused with M1 macrophages had a more severe histological and functional injury, whereas M2 macrophage-induced transfused mice had reduced histological and functional injury. Both M1 and M2 macrophages localized preferentially to the area of injury and maintained their phenotypes even after 4 weeks. The protective effect of M2 macrophages was associated with reduced accumulation and possibly downregulated chemokine and inflammatory cytokine expression of the host infiltrating macrophages. Our findings demonstrate that macrophages not only act as effectors of immune injury but can be induced to provide protection against immune injury.
Studies of mechanisms of disease regulation by CD4؉ CD25 ؉ regulatory T cells (Treg) have been focused on their interaction with effector T cells; however, the possibility that regulation might involve noncognate cells has not been explored in detail. This study investigated the effect of CD4 ؉ CD25 ؉ Treg on macrophage proinflammatory properties and phenotype in vitro and found that they modulate macrophages by inhibiting their activation, leading to reduced proinflammatory cytokine production and a downregulated effector phenotype. For testing the in vivo significance of this effect, CD4 ؉ CD25 ؉ T cells that expressed high levels of Foxp3 were reconstituted into SCID mice after induction of Adriamycin nephropathy, a noncognate model of chronic renal disease. CD4 ؉ CD25 ؉ T cells significantly reduced glomerular and interstitial injury. In addition, there was a significant fall in the number of macrophages in both the glomeruli and interstitium of SCID mice that were reconstituted with Treg as compared with the Adriamycin alone group. Blockade of TGF- using neutralizing antibodies significantly impaired the protective effect of Treg. These findings delineate a TGF--dependent Treg-macrophage inhibitory interaction that can explain cognate-independent protection by Treg.
Objective: To identify the prevalence of coronary risk factors among South Asian Indians in Australia and India. Design: Cross-sectional intercountry comparison. Subjects: Healthy volunteers aged 23-75 y recruited from the Indian community in Sydney Australia (n¼125), and their nominated relatives in India, (n¼125). Results: The two groups were of similar background with over 90% of the group in India being siblings, parents or relatives of the group in Australia. There was no difference in the populations between India and Australia with regard to mean age (40711.5 vs 39710.
Conclusion:The group in Australia (especially women) have a more favourable disease risk profile than those in India. The fact that the groups are of such similar background and partly related, make it unlikely that changes due to migration have a strong genetic bias. In contrast to other studies, the absence here of excessive weight gain on migration may be a key factor in disease risk prevention.
Accurate data about Indigenous child health is vital to enable us to understand its current state, to acknowledge achievements, and to determine how to reduce inequalities between Indigenous and non‐Indigenous children.
We have identified a paucity of national, or nationally representative, data relating to Indigenous child health outcomes, and significant deficiencies in available data.
A coordinated national approach will help address current data limitations, including lack of identification of Indigenous status, lack of currency, and lack of information about specific health disorders affecting Indigenous children.
To ensure that health data collected are relevant and useful, Indigenous communities must have a role in data collection and management.
This comprehensive analysis provides important baseline data for NSW against which future reports can be compared to monitor progress in improving immunisation coverage. Immunisation at the earliest appropriate age should be a public health goal for countries such as Australia where high levels of vaccine coverage at milestone ages have been achieved.
Background/Aim: The investigators were invited into a boys’ high school to assess the lipid risk profile of a single year cohort and advise on how the findings could be incorporated into a healthy lifestyle program. The aim of the study was to investigate the relationship between measures of fatness, ethnicity and cardiac risk factors in a cohort of adolescent boys. Methods: Anthropometric measurements of weight, height, waist and hips were used to calculate body mass index (BMI) and waist to hip ratio (WHR); percent total body fat (%TBF) was estimated by bioelectric impedance analysis. Demographic and behavioral variables were assessed by questionnaire. Total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), apolipoprotein A1 (apoA1), apoliproprotein B (apoB) and insulin were measured in 137 subjects; low-density lipoprotein (LDL-C) was calculated. Results: The study sample was comprised of 139 boys aged 15.7 ± 0.04 years; 46% were Caucasians, 41% were East Asians and 13% were from the Indian subcontinent (South Asian). The crude mean BMI, %TBF and waist measurements were not significantly different between the ethnic groups. South Asians had a higher mean WHR than East Asians (p < 0.004; ANOVA), and also had higher mean %TBF than Caucasians when BMI was adjusted for, and lower BMI than either of the other groups when adjusted for waist (ANCOVA). There was no difference between groups in lipid profiles except for a higher apoB in East Asians compared with Caucasians (p < 0.04). Twenty-two percent of the subjects had TC higher than the desirable level for children (4.5 mmol/l), 7.3% had low HDL-C (<0.9 mmol/l) and 4.3% had high LDL-C (>3.5 mmol/l). Overweight and hypercholesterolemia had individual prevalences of around 20%, while hyperinsulinemia was 48%. Conclusion: The present study confirms that the relationship between BMI and %TBF is dependent on ethnicity, even in adolescent subjects of similar age and gender. The assessment of cardiovascular risk on a school year and age basis would suggest that there are enough affected individuals to support at least a nontargeted intervention which focuses on healthy eating and physical activity.
Partial macrophage depletion starting before but not after ADR protected both renal function and structure in this model of chronic proteinuric renal disease.
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