Sexual Development in Perinatally HIV-Infected Young People: A Systematic Review and Explorative Study.

BACKGROUND: Similar to other young people with a chronic health condition, perinatally HIV-infected (PHIV) adolescents may have an impacted sexual development. OBJECTIVES: This paper aims to compare sexual milestones of PHIV to HIV uninfected peers, through a systematic review (SR) and explorative study. METHODS: We performed a systematic search in 4 electronic databases (Medline, Embase, Web of Science, and Scopus), according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Last search in all databases was performed in May 2021. We included studies that reported on quantitative data of any of the main outcomes and compared PHIV to HIV uninfected control groups. Main outcomes were defined as the occurrence and/or debut age of sexual milestones (falling in love, having been in a romantic relationship, masturbation, kissing, non-genital caressing (feeling or petting, touching), genital caressing (fingering, handjob), giving or receiving oral sex, and penetrative sex (vaginal or anal). We excluded case reports, audits, guidelines, editorials, abstracts, studies that reported on behaviorally infected HIV patients, studies that did not include an HIV uninfected control group and studies that could not be translated to English or Dutch. We used the Agency for Health Care Research and Quality (AHRQ) Checklist for quality assessment. We performed qualitative synthesis of the data. In the explorative study, we compared sexual milestones of PHIV and HIV uninfected controls matched for age, sex, ethnicity and educational level, using a subset of questions of a validated questionnaire. RESULTS: We included eighteen studies in the SR, describing outcomes of an estimated 1,963 participants. Seventeen studies compared the occurrence and/or debut age of intercourse in PHIV and HIV uninfected controls and 4 studies reported on any of the other sexual milestones. The majority of studies found no difference in occurrence (12 of 16 studies) or debut age (6 of 8 studies) of intercourse in PHIV compared to controls. Two of 4 studies reporting on any of the other milestones found no significant differences between PHIV and HIV uninfected controls. In the explorative study, we included ten PHIV participants and 16 HIV uninfected, matched controls. PHIV tended to report a later debut age of sexual milestones than controls (not significant). STRENGTHS AND LIMITATIONS: The SR includes only a small number of studies and few studies report on non-penetrative milestones. The explorative study adds to this review by including non-penetrative milestones and comparing PHIV to HIV-uninfected, well-matched controls. However, the sample size was small. CONCLUSION: PHIV seem to engage in sexual activities and achieve sexual milestones at a similar rate as their HIV uninfected peers, with a tendency of a later start in well treated PHIV. The review was registered in the PROSPERO database (CRD42021252103) and funded by AIDSfonds. AIDSfonds had no role in the study design or interpretations of this study. ter Haar AM, Fieten A, Van den Hof M, et al. Sexual Development in Perinatally HIV-Infected Young People: A Systematic Review and Explorative Study. Sex Med 2022;10:100578.

Health-related quality of life of perinatally HIV-infected young people: a longitudinal study.

Young people perinatally infected with HIV (pHIV) are at risk of a lowered health-related quality of life (HRQOL). Previous evaluation of the NeurOlogical, VIsual and Cognitive performance in HIV-infected Children (NOVICE)-cohort showed no difference in HRQOL between pHIV and matched HIV-uninfected controls (HIV-), yet a higher percentage of pHIV had impaired HRQOL. The aim of this study is to compare the change over time in HRQOL of pHIV to HIV- over a 5-year period. We used the Pediatric Quality of Life Inventory (PedsQL)™ 4.0 to repeat HRQOL assessment. High PedsQL scores indicate good HRQOL. Fifteen/33 (45.5%) pHIV and 17/37 (45.9%) HIV- completed both assessments. At the first assessment, the mean age was 13.1 years (range 8.0-18.4). PHIV scored higher than HIV- on Emotional functioning and on Total scale score. After five years, the mean age was 17.6 years (range 12.1-22.8). PHIV scored higher than HIV- on all scales, except Social functioning. PHIV did not differ significantly from the Dutch norm on either time-point. LMEM showed no difference in change over time for any of the PedsQL scales. In this study, young people with pHIV receiving high-quality health care, including monitoring of HRQOL, remain to experience a good HRQOL.

Fatigue in children and adolescents perinatally infected with human immunodeficiency virus: an observational study.

BACKGROUND: Fatigue is common among adults living with human immunodeficiency virus (HIV) as well as children with a chronic disease (CCD). Fatigue can have disastrous effects on health status, including health related quality of life (HRQOL). Even so, fatigue is underexplored in children and adolescents perinatally infected with HIV (PHIV+) in the Netherlands. The objective of this observational study is to explore fatigue in PHIV+ and its association with their HRQOL. METHODS: We measured HRQOL and fatigue using the Pediatric Quality of Life Inventory™ (PedsQL 4.0) and the PedsQL Multidimensional Fatigue Scale (MFS). The PedsQL MFS encompasses three subscales: general fatigue, sleep/rest fatigue and cognitive fatigue, and a total fatigue score. We compared outcomes of PHIV+ children and adolescents in the Amsterdam University Medical Centre with three groups: 1) HIV-uninfected controls (HIV-) matched for age, sex, region of birth, socioeconomic status and adoption status, 2) CCD, and 3) the general Dutch population. Within the PHIV+ group we explored associations between fatigue and HRQOL. RESULTS: We enrolled 14 PHIV+ (median age 10.2 years [IQR 9.2-11.4]) and 14 HIV-. Compared to CCD, PHIV+ significantly reported less general fatigue (mean difference 13.0, 95% CI 1.3 to 24.8). PHIV+ did not score significantly different on any of the other PedsQL MFS scales compared to HIV-, CCD or the general Dutch population. PHIV children scored relatively low on the cognitive fatigue scale in comparison to HIV-uninfected matched controls, CCD and the general population, although these differences did not reach significance. Among PHIV+, a lower score on total fatigue, general fatigue and cognitive fatigue was associated with a lower HRQOL score. CONCLUSIONS: The results of this study suggest that PHIV children and adolescents do not experience more symptoms of fatigue than their healthy peers. However, PHIV children and adolescents may be more likely to experience cognitive fatigue. Fatigue in PHIV also appears to be associated with children's HRQOL. Further research should confirm these exploratory findings.

Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption.

BACKGROUND: HIV-associated cognitive deficiency in perinatally HIV-infected (PHIV) children has been studied in Western countries in a population of which an increasing proportion has been internationally adopted. Studies often lack an appropriate internationally adopted HIV-uninfected control group, potentially confounding the relationship between HIV and cognitive functioning. This study aims to further elucidate the association between treated HIV infection and cognitive development by addressing the background of international adoption. METHODS: We cross-sectionally studied the impact of HIV on cognition by comparing PHIV children and HIV- uninfected controls, matched for age-, sex-, ethnicity-, socioeconomic status (SES)- and adoption status. We used a standardized neuropsychological test battery to measure intelligence (IQ), and the cognitive domains of processing speed, working memory, executive function, learning ability and visual-motor function and compared outcomes using lineair regression models, adjusted for IQ. We determined cognitive profiles and cognitive impairment by using multivariate normative comparison (MNC) and explored associations with HIV disease- and treatment-related factors. RESULTS: We enrolled fourteen PHIV children (mean age 10.45 years [1.73 SD], 93% adopted from sub-Saharan Africa at a median age of 3.3 years [IQR 2.1-4.2]) and fifteen HIV- uninfected controls. Groups did not clinically nor statistically differ in age, sex, ethnicity, SES, region of birth, adoption status and age at adoption. PHIV scored consistently lower on all cognitive domains and MNC outcomes. Compared to controls, PHIV children had a significant lower IQ (mean 81 [SD 11] versus mean 97 [SD 15], p = 0.005), and a poorer cognitive profile by MNC (Hotelling's T2 mean -4.36 [SD 5.6] versus mean 0.16 [SD 4.5], p = 0.021), not associated with HIV disease- and treatment-related factors. Two PHIV (14%) and one control (7%) were classified as cognitively impaired (p = 0.598). CONCLUSIONS: Findings indicate treated HIV-infection to be independently associated with lower IQ and poorer cognitive profiles in PHIV children, irrespective of a background of international adoption.

Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV.

Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8-18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status. We then compared plasma biomarker levels between groups, and explored associations between plasma/CSF biomarkers and neuroimaging and cognitive outcomes using network analysis. HIV-infected children showed higher plasma levels of C-reactive protein, interferon-gamma, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 than controls. In HIV-infected participants, plasma soluble CD14 was positively associated with microstructural white matter (WM) damage, and plasma D-dimer was negatively associated with WM blood flow. In CSF, IL-6 was negatively associated with WM volume, and neurofilament heavy-chain (NFH) was negatively associated with intelligence quotient and working memory. These markers of ongoing inflammation, immune activation, coagulation, and neuronal damage could be used to further evaluate the pathophysiology and clinical course of cerebral and cognitive deficits in perinatally acquired HIV.

Rapid detection and monitoring of human coronavirus infections.

Human coronaviruses (CoVs) are increasingly recognized as important respiratory pathogens associated with a broad range of clinical diseases. We sought to increase the insight into clinically relevant CoV infections by monitoring antigen concentrations in six confirmed CoV-positive patients using a newly developed assay for rapid detection of CoV OC43 infections. Antigen positivity lasted 3 to 6 days in secondary infections and 13 days in primary infection. CoV infections are clinically diverse, are common, and cannot be diagnosed from clinical symptoms alone.

A molecular epidemiological perspective of rhinovirus types circulating in Amsterdam from 2007 to 2012.

Rhinoviruses (RVs) are frequently detected respiratory viruses that cause mild common cold symptoms, but may also lead to more severe respiratory tract infections. The large number of RV types, classified into species A, B and C, hampers clear insights into the epidemiology and clinical significance of each RV type. The aim of this study was to map the circulation of RV types in the Amsterdam area. RV-positive nasopharyngeal and oropharyngeal samples, collected from 2007 to 2012 in the Academic Medical Centre (Amsterdam, the Netherlands), were typed based on the sequence of the region coding for capsid proteins VP4 and VP2. RV-A, RV-B and RV-C were found in proportions of of 52.4% (334/637), 11.3% (72/637), and 36.2% (231/637), respectively. We detected 129 of the 167 currently classified types. RVs circulated throughout the entire year with a peak in the autumn and a decline in the summer. Some RV types were observed throughout the entire sampling period and others had a more seasonal pattern. Nine RV-A and four RV-B novel provisionally assigned types were identified. This study provides an insight into the molecular epidemiology of RVs in the Amsterdam area. The RVs circulating are diverse and include several provisionally new types.

Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

BACKGROUND: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. METHODS: We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996-2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. RESULTS: HIV VF occurred frequently during the study period (14%-36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12-13 years (odds ratio, 4.26 [95% confidence interval, 1.12-16.28]; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. CONCLUSIONS: HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.

Prevalence of rhinoviruses in young children of an unselected birth cohort from the Netherlands.

Rhinovirus (RV) is a frequent pathogen in young children, eliciting symptoms ranging from common colds to wheezing illnesses and lower respiratory tract infections. The recently identified RV-C seems to be associated with asthma exacerbations and more severe disease, but results vary. We studied the prevalence and severity of infection with RV in an unselected birth cohort. Children with respiratory symptoms entered the symptomatic arm of the cohort and were compared with asymptomatic children. Severity of wheezing and other respiratory symptoms was registered. Respiratory viruses were evaluated using throat and nasopharyngeal swabs on first presentation and after recovery (wheezing children). RV genotyping was performed on RV-PCR positive samples. RV was the most prevalent respiratory virus and was found in 58/140 symptomatic children (41%), 24/96 (25%) control children and 19/74 (26%) wheezing symptomatic children after recovery (p <0.05) and did not differ between wheezing and non-wheezing symptomatic children-respectively, 42% (38/90) and 40% (20/50). RV-A was the most commonly detected species (40/68, 59%), followed by RV-C (22/68, 32%) and RV-B (6/68, 9%). RV-B was more frequently detected in asymptomatic children (5/6, p <0.05). There was no significant difference in the frequency of RV species between wheezing and non-wheezing symptomatic children. Children with RV mono-infection had more severe symptoms, but no association between RV species and severity of disease was seen. In an unselected birth cohort from the Netherlands with mild respiratory disease RV was the most prevalent respiratory virus. RV(-C) infection was not associated with more severe disease or wheezing.

Genetic and antigenic structural characterization for resistance of echovirus 11 to pleconaril in an immunocompromised patient.

Pleconaril is a capsid inhibitor used previously to treat enterovirus infections. A pleconaril-resistant echovirus 11 (E11) strain was identified before pleconaril treatment was given in an immunocompromised patient. The patient was also treated with intravenous Ig (IVIg) for a long period but remained unresponsive. The pleconaril-resistant strains could not be neutralized in vitro, confirming IVIg treatment failure. To identify the basis of pleconaril resistance, genetic and structural analyses were conducted. Analysis of a modelled viral capsid indicated conformational changes in the hydrophobic pocket that could prevent pleconaril docking. Substitutions (V117I, V119M and I188L) in the pleconaril-resistant viruses were found in the pocket region of VP1. Modelling suggested that V119M could confer resistance, most probably due to the protruding sulfate side chain of methionine. Although pleconaril resistance induced in vitro in a susceptible E11 clinical isolate was characterized by a different substitution (I183M), resistance was suggested to also result from a similar mechanism, i.e. due to a protruding sulfate side chain of methionine. Our results showed that resistant strains that arise in vivo display different markers from those identified in vitro and suggest that multiple factors may play a role in pleconaril resistance in patient strains. Based on IVIg treatment failure, we predict that one of these factors could be immune related. Thus, both IVIg and capsid inhibitors target the viral capsid and can induce mutations that can be cross-reactive, enabling escape from both IVIg and the drug. This could limit treatment options and should be investigated further.

Presence of human non-polio enterovirus and parechovirus genotypes in an Amsterdam hospital in 2007 to 2011 compared to national and international published surveillance data: a comprehensive review.

Enteroviruses (EV) and human parechoviruses (HPeV) are endemic worldwide. These infections are a constant cause of hospitalisation and severe disease, predominantly in young children and infants. Coordinated monitoring and surveillance are crucial to control these infections. We have monitored EV and HPeV epidemiology in Amsterdam from 2007 to 2011 with real-time RT-PCR and direct genotyping, facilitating highly sensitive surveillance. Moreover, we conducted a literature survey of existing surveillance data for comparison. Only 14 studies were identified. While HPeV1 was most frequently detected in Amsterdam, EV-B viruses dominated nationally and internationally. Furthermore, the top 10 strains detected differed yearly and per study. However, detection and typing methods were too varied to allow direct comparison and comprehension of the worldwide distribution and circulation patterns of the different genotypes. This limited a direct response to anticipate peaks. Uniform European monitoring programmes are essential to aid prediction of outbreaks and disease management.

Clinical relevance of positive human parechovirus type 1 and 3 PCR in stool samples.

Human parechoviruses (HPeV) cause symptoms ranging from severe neonatal infections to mild gastrointestinal and respiratory disease. Use of PCR and genotyping has markedly improved the detection rate of HPeV but has simultaneously raised questions about the clinical relevance of positive tests. This retrospective study correlates positive HPeV1 or HPeV3 PCR tests in stools from children with their symptoms to determine clinical relevance. Children with HPeV1- or HPeV3-positive stool samples, as detected by real time RT-PCR and direct genotyping, between 2004 and 2008 were selected. Clinical data were retrospectively collected from the patient's files and results were compared. One hundred and thirty-eight children with positive HPeV1 (n = 112) or HPeV3 (n = 26) stool samples were identified. Significantly more HPeV3-infected children were neonates or infants younger than 6 months of age. Meningitis or sepsis-like illnesses were diagnosed most frequently and were found in significantly younger children. Almost half of HPeV1-infected children had an underlying disease. Mild gastrointestinal disease was seen most frequently in these children. There was no clear correlation between viral load (Ct value) and severity of symptoms. In conclusion, HPeV3 detected by PCR in stool samples is associated with clinically relevant disease. For HPeV1, a positive stool sample is mainly associated with symptoms in children with underlying disease.

Human parechovirus infections in Dutch children and the association between serotype and disease severity.

BACKGROUND: Human parechoviruses (HPeVs) are members of the family Picornaviridae and are classified into 3 known serotypes: HPeV1, HPeV2, and the recently identified HPeV3. HPeV1 and HPeV2 infections are most commonly associated with mild respiratory or gastrointestinal symptoms and occasionally with severe disease conditions, such as flaccid paralysis and encephalitis. HPeV3 infection has been associated with transient paralysis and neonatal infection and has until now only been reported in Japan and Canada. METHODS: Culture isolates considered to be enterovirus on the basis of cell culture but that were found to be enterovirus negative by 5' untranslated region reverse-transcriptase polymerase chain reaction (5'UTR RT-PCR) during the period December 2000 through January 2005 were selected. Isolates were tested by HPeV 5'UTR RT-PCR and were genotyped by sequencing the VP1 region. Phylogenetic analysis was performed, and the association with clinical symptoms was established. RESULTS: Thirty-seven (12%) of the 303 isolates that tested positive for enterovirus by cell culture were in fact HPeV. The majority of the HPeV-positive isolates (n = 27) could be identified as HPeV1. The remaining 10 isolates, which were grown from samples obtained in 2001, 2002, and 2004, could be typed as the recently identified HPeV3. HPeV was exclusively detected in children aged < 3 years. Children infected with HPeV3 were significantly younger than children infected with HPeV1, and sepsis-like illness and central nervous system involvement were more frequently reported in children infected with HPeV3. CONCLUSIONS: We report HPeV infections in young children during the period of 2000-2005 and show an association between HPeV3 infection and sepsis-like illness and central nervous system involvement in neonates.

Primary autoimmune neutropenia in children: a study of neutrophil antibodies and clinical course.

BACKGROUND AND OBJECTIVES: Primary autoimmune neutropenia (AIN) in children is characterized by severe neutropenia, but mild bacterial infections and a spontaneous resolution. Neutrophil autoantibodies are involved in the disease. The precise relationship between the specificity and level of reactivity of the antibodies with the absolute neutrophil count and frequency of infections is not known. To obtain a better insight into this relationship, we performed a follow-up study in 15 patients with primary AIN. In addition, we performed two different neutrophil antibody tests to evaluate their sensitivity and specificity. MATERIALS AND METHODS: Blood samples from 15 children were tested for neutrophil antibodies, at different time-points during the disease, by using the indirect granulocyte immunofluorescence test (GIFT) and the monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA) assay. Clinical data related to the occurrence of bacterial infections and treatment, and neutrophil counts were collected. RESULTS: Early in the disease, antibodies with pan-FcRIIIb specificity were detected, and HNA-1a or HNA-1b specificity of the antibodies developed over time. The sensitivity and specificity of neutrophil antibody detection tests were higher in the GIFT than in the MAIGA assay. Variables predicting time of recovery from neutropenia were not found. Prophylactic antibiotics led to the almost complete disappearance of infections. CONCLUSIONS: In patients with primary neutropenia, neutrophil antibody specificity changes over time. Prophylactic antibiotics do benefit the patients.

Pyelonephritis caused by Actinobaculum schaalii in a child with pyeloureteral junction obstruction.

Reported here is the case of a 5-year old boy with a pyeloureteral junction (PUJ) obstruction and pyelonephritis caused by Actinobaculum schaalii, an Actinomyces-like organism. Pyelonephritis or any other urinary tract infection caused by Actinobaculum schaalii has not been described in children before. The patient responded well to pyeloplasty in combination with antibiotic treatment.

Effect of interleukin 10 on the release of the CXC chemokines growth related oncogene GRO-alpha and epithelial cell-derived neutrophil activating peptide (ENA)-78 during human endotoxemia.

Pretreatment with interleukin (IL)-10 inhibited the release of growth-related oncogene GRO-alpha but not of epithelial-cell derived neutrophil activating protein (ENA)-78, after injection of lipopolysaccharide (LPS) into healthy humans. In vitro, IL-10 dose-dependently attenuated LPS-induced release of both GRO-alpha and ENA-78 in whole blood and in cultures of isolated polymorphonuclear and mononuclear cells.

[Activated protein C, coagulation, inflammation, and treatment of severe sepsis]. / Geactiveerd proteïne C, stolling, ontsteking en de behandeling van ernstige sepsis.

During the past 20 years several treatments designed to reduce inflammatory responses to sepsis have been unsuccessful. Sepsis results from a generalised inflammatory and procoagulant response to an infection. Activated protein C, a component of the anticoagulant system, is an anti-thrombotic serine protease with anti-inflammatory properties. A recently published study reported the results of a large clinical trial in which recombinant human activated protein C significantly reduced mortality in patients with severe sepsis. Treatment with activated protein C also reduced circulating D-dimer and IL-6 levels, which are markers of coagulation activation and inflammation. There are several reasons why activated protein C could be effective in sepsis. Firstly, reduced levels of protein C are found during sepsis and are associated with an increased risk of death. Secondly, activated protein C can directly inhibit factors Va and VIIIa, resulting in decreased thrombin formation. Finally, activated protein C can reduce plasminogen activator inhibitor I, thereby stimulating fibrinolysis. In addition to these effects on thrombin formation, activated protein C directly reduces pro-inflammatory responses by as yet unknown mechanisms.

Proinflammatory effects of IL-10 during human endotoxemia.

IL-10 is considered a potent antiinflammatory cytokine that strongly inhibits the production of proinflammatory cytokines. Recent studies have suggested that IL-10 also has immunostimulatory properties on CD4+, CD8+ T cells, and/or NK cells, resulting in increased IFN-gamma production. To determine the effect of IL-10 on IFN-gamma production and related inflammatory responses in humans, 16 healthy subjects received a bolus i.v. injection of LPS (4 ng/kg) in combination with either placebo or recombinant human IL-10 (25 microg/kg), administered just before or 1 h after LPS. IL-10 treatment, particularly when administered after LPS, enhanced LPS-induced IFN-gamma release, as well as the release of the IFN-gamma-dependent chemokines IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma, while inhibiting or not influencing the production of IFN-gamma-inducing cytokines. In addition, IL-10 treatment enhanced activation of CTLs and NK cells after LPS injection, as reflected by increased levels of soluble granzymes. These data indicate that high-dose IL-10 treatment in patients with inflammatory disorders can be associated with undesired proinflammatory effects.

Interleukin 10 inhibits the release of CC chemokines during human endotoxemia.

Sixteen healthy subjects were intravenously injected with lipopolysaccharide (LPS), once with placebo and once with recombinant human interleukin (IL)-10 (25 microgram/kg), to determine the effect of IL-10 on LPS-induced production of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1. LPS induced transient increases in serum MIP-1alpha, MIP-1beta, and MCP-1. Pretreatment with IL-10 inhibited LPS-induced release of MIP-1alpha, MIP-1beta, and MCP-1. In whole blood in vitro, the IL-10-induced inhibition of MIP-1alpha and MIP-1beta release was equally potent in the presence or absence of an anti-tumor necrosis factor (TNF) antibody. Although isolated peripheral blood mononuclear cells produced more MIP-1alpha and MIP-1beta than neutrophils, the latter cells were more sensitive to the inhibiting effect of IL-10. IL-10 attenuates LPS-induced production of CC chemokines in human endotoxemia, whereby in vitro experiments suggest that, in the case of MIP-1alpha and MIP-1beta release, this effect is independent from an inhibitory effect on TNF production.