Direct administration of the non-competitive interleukin-1 receptor antagonist rytvela transiently reduced intrauterine inflammation in an extremely preterm sheep model of chorioamnionitis

Background Intraamniotic inflammation is associated with up to 40% of preterm births, most notably in deliveries occurring prior to 32 weeks’ gestation. Despite this, there are few treatment options allowing the prevention of preterm birth and associated fetal injury. Recent studies have shown that the small, non-competitive allosteric interleukin (IL)-1 receptor inhibitor, rytvela, may be of use in resolving inflammation associated with preterm birth (PTB) and fetal injury. We aimed to use an extremely preterm sheep model of chorioamnionitis to investigate the anti-inflammatory efficacy of rytvela in response to established intra-amniotic (IA) lipopolysaccharide (LPS) exposure. We hypothesized that rytvela would reduce LPS-induced IA inflammation in amniotic fluid (AF) and fetal tissues. Methods Sheep with a single fetus at 95 days gestation (estimated fetal weight 1.0 kg) had surgery to place fetal jugular and IA catheters. Animals were recovered for 48 hours before being randomized to either: i) IA administration of 2 ml saline 24 hours before 2 ml IA and 2 ml fetal intravenous (IV) administration of saline (Saline Group, n = 7); ii) IA administration of 10 mg LPS in 2 ml saline 24 hours before 2 ml IA and 2 ml fetal IV saline (LPS Group, n = 10); 3) IA administration of 10 mg LPS in 2 ml saline 24 hours before 0.3 mg/fetal kg IA and 1 mg/fetal kg fetal IV rytvela in 2 ml saline, respectively (LPS + rytvela Group, n = 7). Serial AF samples were collected for 120 h. Inflammatory responses were characterized by quantitative polymerase chain reaction (qPCR), histology, fluorescent immunohistochemistry, enzyme-linked inmmunosorbent assay (ELISA), fluorescent western blotting and blood chemistry analysis. Results LPS-treated animals had endotoxin and AF monocyte chemoattractant protein (MCP)-1 concentrations that were significantly higher at 24 hours (immediately prior to rytvela administration) relative to values from Saline Group animals. Following rytvela administration, the average MCP-1 concentrations in the AF were significantly lower in the LPS + rytvela Group relative to in the LPS Group. In delivery samples, the expression of IL-1β in fetal skin was significantly lower in the LPS + rytvela Group compared to the LPS Group. Conclusion A single dose of rytvela was associated with partial, modest inhibition in the expression of a panel of cytokines/chemokines in fetal tissues undergoing an active inflammatory response.

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Impact of smoking and fetal gender on preterm delivery

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174420000999 ◽

2020 ◽

pp. 1-6

Author(s):

Veronika Günther ◽

Ibrahim Alkatout ◽

Alexandra Stein ◽

Nicolai Maass ◽

Alexander Strauss ◽

...

Keyword(s):

Risk Factors ◽

Preterm Birth ◽

Preterm Delivery ◽

Preterm Infants ◽

Preterm Births ◽

World Health ◽

Smoking During Pregnancy ◽

Fetal Gender ◽

Extremely Preterm ◽

Heavy Smokers

Abstract According to the World Health Organization, smoking is the most important risk factor for adverse pregnancy outcomes in industrialized nations. We aimed to establish how fetal gender and smoking interact with regard to perinatal outcomes, especially preterm delivery. Data from 220,339 singleton pregnancies, obtained from the German Perinatal Survey in Schleswig-Holstein and registered between 2004 and 2017 were analyzed in regard to smoking behavior, fetal gender, and preterm delivery. The rate of preterm births was directly proportional to the women’s consumption of nicotine. The rate of preterm deliveries was 6.8% among nonsmokers, and 13.2% in women who were very heavy smokers (≥22 cigarettes/day). Very heavy smoking (≥22 cigarettes/day) had a marked impact on extremely preterm births (<28 weeks of gestation) and very preterm births (28–31 weeks of gestation). Preterm births increased by 1.2% from heavy smokers to very heavy smokers; the differences between the other groups ranged between 0.1% and 0.4%. Fetal gender also had an impact on preterm birth: male infants were predominant in nearly all groups of women who delivered preterm infants. Smoking during pregnancy and male gender are both risk factors for preterm delivery. Fetal gender should be given greater attention as one of the several risk factors of preterm birth. Due to the high rate of morbidity among preterm infants and enormous costs for the healthcare system, women should be encouraged to cease or at least reduce smoking during pregnancy.

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Preterm birth and sustained inflammation: consequences for the neonate

Seminars in Immunopathology ◽

10.1007/s00281-020-00803-2 ◽

2020 ◽

Vol 42 (4) ◽

pp. 451-468 ◽

Cited By ~ 3

Author(s):

Alexander Humberg ◽

◽

Ingmar Fortmann ◽

Bastian Siller ◽

Matthias Volkmar Kopp ◽

...

Keyword(s):

Preterm Birth ◽

Preterm Infants ◽

Defense Mechanisms ◽

Preterm Births ◽

Immune Defense ◽

Term Outcome ◽

Long Term Outcome ◽

Organ Systems ◽

Extremely Preterm ◽

Extremely Preterm Infants

Abstract Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome.

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Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-04249-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

J. Klumper ◽

B. M. Kazemier ◽

J. V. Been ◽

K. W. M. Bloemenkamp ◽

M. A. de Boer ◽

...

Keyword(s):

Preterm Birth ◽

The Netherlands ◽

Risk Mitigation ◽

Preterm Births ◽

Multiple Pregnancies ◽

Very Preterm ◽

Extremely Preterm ◽

Using Data ◽

Extremely Preterm Birth ◽

Singleton Pregnancies

Abstract Background The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. Methods Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015–2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. Results The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015–2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). Conclusion This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

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Preterm birth, stillbirth and early neonatal mortality during the Danish COVID-19 lockdown

European Journal of Pediatrics ◽

10.1007/s00431-021-04297-4 ◽

2021 ◽

Author(s):

Paula L. Hedley ◽

Gitte Hedermann ◽

Christian M. Hagen ◽

Marie Bækvad-Hansen ◽

Henrik Hjalgrim ◽

...

Keyword(s):

Preterm Birth ◽

Perinatal Mortality ◽

Birth Rate ◽

Preterm Births ◽

Extended Period ◽

Stillbirth Rate ◽

Early Neonatal Mortality ◽

Extremely Preterm ◽

Preterm Birth Rate ◽

Extremely Preterm Birth

AbstractUsing provisional or opportunistic data, three nationwide studies (The Netherlands, the USA and Denmark) have identified a reduction in preterm or extremely preterm births during periods of COVID-19 restrictions. However, none of the studies accounted for perinatal deaths. To determine whether the reduction in extremely preterm births, observed in Denmark during the COVID-19 lockdown, could be the result of an increase in perinatal deaths and to assess the impact of extended COVID-19 restrictions, we performed a nationwide Danish register-based prevalence proportion study. We examined all singleton pregnancies delivered in Denmark during the COVID-19 strict lockdown calendar periods (March 12–April 14, 2015-2020, N = 31,164 births) and the extended calendar periods of COVID-19 restrictions (February 27–September 30, 2015-2020, N = 214,862 births). The extremely preterm birth rate was reduced (OR 0.27, 95% CI 0.07 to 0.86) during the strict lockdown period in 2020, while perinatal mortality was not significantly different. During the extended period of restrictions in 2020, the extremely preterm birth rate was marginally reduced, and a significant reduction in the stillbirth rate (OR 0.69, 0.50 to 0.95) was observed. No changes in early neonatal mortality rates were found.Conclusion: Stillbirth and extremely preterm birth rates were reduced in Denmark during the period of COVID-19 restrictions and lockdown, respectively, suggesting that aspects of these containment and control measures confer an element of protection. The present observational study does not allow for causal inference; however, the results support the design of studies to ascertain whether behavioural or social changes for pregnant women may improve pregnancy outcomes. What is Known:• The aetiologies of preterm birth and stillbirth are multifaceted and linked to a wide range of socio-demographic, medical, obstetric, foetal, psychosocial and environmental factors.• The COVID-19 lockdown saw a reduction in extremely preterm births in Denmark and other high-income countries. An urgent question is whether this reduction can be explained by increased perinatal mortality. What is New:• The reduction in extremely preterm births during the Danish COVID-19 lockdown was not a consequence of increased perinatal mortality, which remained unchanged during this period.• The stillbirth rate was reduced throughout the extended period of COVID-19 restrictions.

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Pathogenesis to Treatment: Preventing Preterm Birth Mediated by Infection

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/s1064744997000173 ◽

1997 ◽

Vol 5 (2) ◽

pp. 106-114 ◽

Cited By ~ 2

Author(s):

James A. McGregor ◽

Janice I. French

Keyword(s):

Preterm Birth ◽

Preterm Labor ◽

Inflammatory Responses ◽

Systemic Treatment ◽

Preterm Births ◽

Host Responses ◽

Obstetrical Care ◽

Preterm Premature Rupture ◽

Genital Tract Infections ◽

Tract Infections

Prevention of preterm birth and subsequent newborn immaturity is a primary goal of obstetrical care worldwide. Accumulated evidence shows that 1) as many as 25–50% of preterm births are caused by common genital tract infections and subsequent maternal/fetal inflammatory responses; 2) microbial and maternal host factors (phospholipases, proteases, etc.) play roles in preterm labor and preterm premature rupture of membranes (pPROM); 3) integrated aspects of maternal and fetal host responses (inflammation, altered immune adaptations, endocrine and paracrine mechanisms) play increasingly understood roles in premature activation of parturition; and 4) identification and systemic treatment of common genitourinary infections, most importantly bacterial vaginosis (BV), reduce the risks of preterm delivery and PROM.

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Association between maternal country of birth and preterm birth: A population-based register study of 910,752 deliveries

Scandinavian Journal of Public Health ◽

10.1177/1403494821992894 ◽

2021 ◽

pp. 140349482199289

Author(s):

Tiril Tingleff ◽

Sari Räisänen ◽

Åse Vikanes ◽

Leiv Sandvik ◽

Katariina Laine

Keyword(s):

Preterm Birth ◽

Preterm Births ◽

Population Based ◽

Sub Saharan Africa ◽

Country Of Birth ◽

Very Preterm ◽

Extremely Preterm ◽

Study Population ◽

Sub Saharan ◽

Extremely Preterm Birth

Aims: The aim of this study was to analyse associations between maternal country of birth and preterm birth among women giving birth in Norway. Methods: A population-based register study was conducted employing official national databases in Norway. All singleton births, with neonates without major anomalies, between 1999 and 2014 were included ( N=910,752). We estimated odds ratios (ORs) for extremely preterm birth (<28 weeks gestation), very preterm birth (28–33 weeks gestation) and late preterm birth (34–36 weeks gestation) by maternal country of birth. We conducted multivariable regression analyses, adjusting for maternal, obstetric and socio-economic confounders. Results: For extremely preterm births (0.4% of the study population), women with an unknown country of birth (adjusted OR (aOR)=3.09; 95% confidence interval (CI) 2.26–4.22) and women born in sub-Saharan Africa (aOR=1.66; CI 1.40–1.96) had the highest ORs compared to Norwegian-born women. For very preterm births (1.2% of the study population), women with an unknown country of birth (aOR=1.72; CI 1.36–2.18) and women born in South Asia (aOR=1.48; CI 1.31–1.66) had the highest ORs. For late preterm births (3.8% of the study population), women born in East Asia Pacific/Oceania (aOR=1.33; CI 1.25–1.41) and South Asia (aOR=1.30; CI 1.21–1.39) had the highest ORs. Conclusions: After adjusting for maternal, obstetric and socio-economic risk factors, maternal country of birth remained significantly associated with preterm birth. Women with an unknown country of birth and women born in sub-Saharan Africa were found to be at increased risk of extremely preterm birth.

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Correlation between placental pathology and neonatal morbidity: a case-control study

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20170390 ◽

2017 ◽

Vol 6 (2) ◽

pp. 599

Author(s):

Anna Kornete ◽

Natalija Vedmedovska ◽

Solvita Blazuka

Keyword(s):

Preterm Birth ◽

Case Control Study ◽

Preterm Births ◽

Neonatal Morbidity ◽

Case Control ◽

Late Preterm ◽

Very Preterm ◽

Very Preterm Birth ◽

Extremely Preterm ◽

Control Study

Background: Preterm births occur in approximately 12% of pregnancies worldwide and in 5.6% of pregnancies in Latvia, and the incidence has increased. Prematurity poses the major challenge in perinatology and pediatrics, accounting for 75% of perinatal mortalities and 50% of long-term complication. The placenta is a unique organ in explaining the incomprehensible pathogenesis of prematurity.Methods: The retrospective case-control study was conducted to determine placental histological and microbiological findings associated with gestational age and neonatal morbidity.Results: Histological chorioamnionitis was the most prevalent lesion in extremely preterm and very preterm birth groups compared with moderate to late preterm and term birth groups (P=0.027). A higher rate of funisitis was detected among extremely preterm and very preterm birth cases (P=0.001). Microbiological examination of placentas in preterm birth cases most commonly revealed Streptococcus agalactiae, Staphylococcus epidermidis, Staphylococcus haemolyticus. Umbilical cord vessels thrombosis and placental thrombotic vasculopathy were found mostly in moderate to late preterm birth category (P=0.032; P=0.008, respectively). Intrauterine growth restriction was linked to chorionic villous edema (P=0.007) and chorionic villous fibrinoid necrosis (P=0.014). Chorion-decidual hemorrhage and deciduitis were significantly associated with respiratory distress syndrome (P=0.036; P=0.022, respectively). Chorion-decidual hemorrhage was the main predisposing factor for hypoxic-ischemic encephalopathy (P=0.058).Conclusions: Comprehension of the pathogenic mechanisms of prematurity of the placenta and preterm births, and the impact of placental prematurity on neonatal morbidity may lead to improved prenatal diagnostic and enhanced preventive care for both the mother and the child.

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Predictors of singleton preterm birth using multinomial regression models accounting for missing data: A birth registry-based cohort study in northern Tanzania

PLoS ONE ◽

10.1371/journal.pone.0249411 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249411

Author(s):

Innocent B. Mboya ◽

Michael J. Mahande ◽

Joseph Obure ◽

Henry G. Mwambi

Keyword(s):

Preterm Birth ◽

Regression Models ◽

Perinatal Death ◽

Placenta Previa ◽

Preterm Births ◽

Late Preterm ◽

Multinomial Regression ◽

Birth Registry ◽

Northern Tanzania ◽

Extremely Preterm

Background Preterm birth is a significant contributor of under-five and newborn deaths globally. Recent estimates indicated that, Tanzania ranks the tenth country with the highest preterm birth rates in the world, and shares 2.2% of the global proportion of all preterm births. Previous studies applied binary regression models to determine predictors of preterm birth by collapsing gestational age at birth to <37 weeks. For targeted interventions, this study aimed to determine predictors of preterm birth using multinomial regression models accounting for missing data. Methods We carried out a secondary analysis of cohort data from the KCMC zonal referral hospital Medical Birth Registry for 44,117 women who gave birth to singletons between 2000-2015. KCMC is located in the Moshi Municipality, Kilimanjaro region, northern Tanzania. Data analysis was performed using Stata version 15.1. Assuming a nonmonotone pattern of missingness, data were imputed using a fully conditional specification (FCS) technique under the missing at random (MAR) assumption. Multinomial regression models with robust standard errors were used to determine predictors of moderately to late ([32,37) weeks of gestation) and very/extreme (<32 weeks of gestation) preterm birth. Results The overall proportion of preterm births among singleton births was 11.7%. The trends of preterm birth were significantly rising between the years 2000-2015 by 22.2% (95%CI 12.2%, 32.1%, p<0.001) for moderately to late preterm and 4.6% (95%CI 2.2%, 7.0%, p = 0.001) for very/extremely preterm birth category. After imputation of missing values, higher odds of moderately to late preterm delivery were among adolescent mothers (OR = 1.23, 95%CI 1.09, 1.39), with primary education level (OR = 1.28, 95%CI 1.18, 1.39), referred for delivery (OR = 1.19, 95%CI 1.09, 1.29), with pre-eclampsia/eclampsia (OR = 1.77, 95%CI 1.54, 2.02), inadequate (<4) antenatal care (ANC) visits (OR = 2.55, 95%CI 2.37, 2.74), PROM (OR = 1.80, 95%CI 1.50, 2.17), abruption placenta (OR = 2.05, 95%CI 1.32, 3.18), placenta previa (OR = 4.35, 95%CI 2.58, 7.33), delivery through CS (OR = 1.16, 95%CI 1.08, 1.25), delivered LBW baby (OR = 8.08, 95%CI 7.46, 8.76), experienced perinatal death (OR = 2.09, 95%CI 1.83, 2.40), and delivered male children (OR = 1.11, 95%CI 1.04, 1.20). Maternal age, education level, abruption placenta, and CS delivery showed no statistically significant association with very/extremely preterm birth. The effect of (<4) ANC visits, placenta previa, LBW, and perinatal death were more pronounced on the very/extremely preterm compared to the moderately to late preterm birth. Notably, extremely higher odds of very/extreme preterm birth were among the LBW babies (OR = 38.34, 95%CI 31.87, 46.11). Conclusions The trends of preterm birth have increased over time in northern Tanzania. Policy decisions should intensify efforts to improve maternal and child care throughout the course of pregnancy and childbirth towards preterm birth prevention. For a positive pregnancy outcome, interventions to increase uptake and quality of ANC services should also be strengthened in Tanzania at all levels of care, where several interventions can easily be delivered to pregnant women, especially those at high-risk of experiencing adverse pregnancy outcomes.

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Sphingosine Kinase: A Novel Putative Target for the Prevention of Infection-Triggered Preterm Birth

Obstetrics and Gynecology International ◽

10.1155/2013/302952 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Vibhuti Vyas ◽

Charles R. Ashby ◽

Sandra E. Reznik

Keyword(s):

Preterm Birth ◽

Preterm Births ◽

Sphingosine Kinase ◽

The United States ◽

High Rate ◽

Survival Pathways ◽

Extremely Preterm ◽

Sphingosine 1 Phosphate ◽

Potent Vasoconstrictor

Preterm birth is defined as any delivery before 37 complete weeks of gestation. It is a universal challenge in the field of obstetrics owing to its high rate of mortality, long-term morbidity, associated human suffering and economic burden. In the United States, about 12.18% deliveries in 2009 were preterm, producing an exorbitant cost of $5.8 billion. Infection-associated premature rupture of membranes (PROM) accounts for 40% of extremely preterm births (<28 weeks of gestation). Major research efforts are directed towards improving the understanding of the pathophysiology of preterm birth and ways to prevent or at least postpone delivery. Endothelin-1 (ET-1) is a potent vasoconstrictor that plays a significant role in infection-triggered preterm birth. Its involvement in a number of pathological mechanisms and its elevation in preterm delivered amniotic fluid samples implicate it in preterm birth. Sphingosine kinase (SphK) is a ubiquitous enzyme responsible for the production of sphingosine-1-phosphate (S1P). S1P acts as second messenger in a number of cell proliferation and survival pathways. SphK is found to play a key role in ET-1 mediated myometrial contraction. This review highlights SphK as a prospective target with great potential to prevent preterm birth.

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Pulmonary Health Effects Following Repeated Exposure and Cessation to Wintertime Particulate Matter from California and China

10.21203/rs.2.20370/v1 ◽

2020 ◽

Author(s):

Wanjun Yuan ◽

Sandra C Velasquez ◽

Ching-wen Wu ◽

Ciara C Fulgar ◽

Qi Zhang ◽

...

Keyword(s):

Particulate Matter ◽

Inflammatory Responses ◽

Quantitative Polymerase Chain Reaction ◽

Interleukin 1 ◽

Strong Association ◽

Time Lag ◽

Geographic Region ◽

Equal Mass ◽

Necrosis Factor Alpha ◽

Pm 2.5

Abstract Background: Epidemiological studies show a strong association between fine particulate matter (PM 2.5 ) air pollution and adverse pulmonary effects. While PM concentration can vary by time and location, PM toxicity has been most recently linked to both physicochemical composition and exposure scenario. To study the relevance of particle characteristics to toxicity, winter PM 2.5 samples were obtained from three geographically similar regions (Sacramento, California, USA; Jinan, Shandong, China; and Taiyuan, Shanxi, China), with typically high atmospheric PM 2.5 emissions. PM extract samples (PM CA , PM SD , and PM SX , respectively) were administered by oropharyngeal aspiration (OPA) to different groups of BALB/C mice, at equal mass concentrations [0 (water vehicle control only) or 20 µg/50 µL], on five different occasions over a two-week period, for a cumulative PM dose of 0 or 100 µg/mouse. Mice were necropsied on Days 1, 2 and 4 after the final exposure, and pulmonary effects were evaluated by bronchoalveolar lavage (BAL), histopathology, quantitative polymerase chain reaction tests, and enzyme-linked immunosorbent assays. Results: Unique differences were noted in the chemical composition for each geographic region with PM SX containing the highest concentration of sulfates (organic and inorganic). A systematic examination of the time lag effects of repeated PM exposure demonstrated unique differences. In mice administered PM SX versus the control, BAL neutrophilia, alveolitis, and bronchiolitis were observed on Days 1 and 4. By Day 4, PM SX -exposed mice also exhibited increased gene expression for multiple inflammatory cytokines/chemokines (interleukin 1 beta, tumor necrosis factor alpha, chemokine C-X-C motif ligands-3 and -5), and increased levels of monocyte chemoattractant protein-1 relative to control-, PM CA -, or PM SD -exposed mice . Conclusions: Direct comparison of the toxic effects of three geographically different PM samples on an equal mass basis demonstrate unique pathobiology with increasing lag time post-exposure. Higher sulfate levels in PM SX versus PM CA and PM SD may contribute to the greater inflammatory responses noted that progressed over time.

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