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The effect of trovafloxacin, ciprofloxacin and ceftriaxone on cytokine production of human peripheral blood mononuclear cells (PBMCs) was examined. PBMC responses were measured after stimulation with lipopolysaccharide (LPS), lipoteichoic acid (LTA) or killed or viable Streptococcus pneumoniae and Haemophilus influenzae. Trovafloxacin inhibited the production of tumour necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and IL-8 by PBMCs after stimulation with either LPS or LTA by 83%. Similar inhibition occurred in PBMCs incubated with killed or live bacteria and trovafloxacin, but not with ciprofloxacin or ceftriaxone. The relevance of this in vitro observation was explored by examining TNF-alpha and IL-6 responses in trovafloxacin-treated mice. Serum concentrations of both cytokines 1 h after LPS challenge were 95% less than serum concentrations in mice that were not given trovafloxacin. Reverse transcription- polymerase chain reaction studies of the mechanisms determining cytokine down-regulation demonstrated that trovafloxacin reduced TNF-alpha, IL-1beta and IL-6 mRNA to levels similar to those of unstimulated cells. These observations indicate that trovafloxacin can consistently and significantly reduce production of cytokines that play an important role in sepsis. In vitro, this effect can occur in the presence of bacteriolysis and is associated with inhibition of transcription of cytokine genes. [ABSTRACT FROM AUTHOR]

Examines the role of serum interleukin-6 (IL-6) as an indirect mediator of capillary permeability and marker for systemic inflammation in early postoperative pleural effusions. Association of congenital heart surgeries with large pleural effusions; Factors affecting the amount and duration of pleural effusions; Relation between immediate postbypass serum IL-6 levels and a number of days of postoperative fever.

Objectives: To describe the demographic and clinical characteristics of children for whom claims were filed with the National Vaccine Injury Compensation Program (VICP) alleging seizure disorder and/or encephalopathy as a vaccine injury., Study Design: The National VICP within the Department of Health and Human Services compensates individuals who develop medical problems associated with a covered immunization. We retrospectively reviewed medical records of children younger than 2 years of age with seizures and/or encephalopathy allegedly caused by an immunization, where a claim was filed in the VICP between 1995 through 2005., Results: The VICP retrieved 165 claims that had sufficient clinical information for review. Approximately 80% of these alleged an injury associated with whole-cell diphtheria, pertussis (whooping cough), and tetanus or tetanus, diphtheria toxoids, and acellular pertussis vaccine. Pre-existing seizures were found in 13% and abnormal findings on a neurologic examination before the alleged vaccine injury in 10%. A final diagnostic impression of seizure disorder was established in 69%, of whom 17% (28 patients) had myoclonic epilepsy, including possible severe myoclonic epilepsy of infancy. Specific conditions not caused by immunization, such as tuberous sclerosis and cerebral dysgenesis, were identified in 16% of subjects., Conclusion: A significant number of children with alleged vaccine injury had pre-existing neurologic or neurodevelopmental abnormalities. Among those developing chronic epilepsy, many had clinical features suggesting genetically determined epilepsy. Future studies that include genotyping may allow more specific therapy and prognostication, and enhance public confidence in vaccination., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To understand the extent of off-label prescribing among pediatrics, the study assesses the prescribing patterns of antidepressants in ambulatory settings., Methods: A cross-sectional analysis was conducted using the National Ambulatory Medical Care Survey from 2000 to 2006. The prevalence of off-label prescribing of antidepressants was estimated, and predictive factors were evaluated., Participants: Children and adolescents aged 6-18 years to private physicians' offices., Main Outcome Measures: Prevalence of antidepressant prescriptions including FDA and non-FDA-approved indications, types of antidepressants prescribed, and factors associated with off-label prescribing., Results: Our study population made 18 646 visits to private physicians' offices, representing about 667 million weighted visits during the study period. The mean age of the patients was 12.2 years (SD = 3.7), and majority of the visits were made by White people (73.1%). Of all visits, 3.7% (95%CI: 3.2%-4.2%) were associated with antidepressants. The most prevalent form of antidepressants prescribed were selective serotonin reuptake inhibitors (63.7%). Only 9.2% of the visits were associated with FDA-approved indications. Visits made to pediatricians (adjusted OR = 2.4; 95%CI: 1.1-5.1), family physicians, and other offices (adjusted OR = 1.9; 95%CI: 1.2-3.1) were more likely to be associated with off-label prescribing as compared with visits to a psychiatrist's office., Conclusions: The study observed a very high prevalence of off-label antidepressant prescribing patterns among children and adolescents in US ambulatory care settings. Coordinated efforts should be placed to evaluate the potential reasons and ramifications of antidepressant off-label prescribing to guard patients' safety., (Copyright © 2011 John Wiley & Sons, Ltd.)

The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 (HIV-1) infection to the Acquired Immunodeficiency Syndrome (AIDS) was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg) cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections, and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child. While effective anti-retroviral therapy (ART) has enhanced survival, wasting is still an independent predictor of survival and a major presenting symptom. Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants. Nutritional intervention after 6 months of age appears to be largely ineffective. A meta analysis of randomized, controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to formula alone. Pilot studies have shown that probiotic bacteria given as a supplement have improved growth and protected against loss of CD4+ T cells. The recognition that normal bacterial flora prime neonatal immune response and that abnormal flora have a profound impact on metabolism has generated insight into potential mechanisms of gut dysfunction in many settings including HIV-1 infection. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection. Probiotic bacteria have proven active against bacterial vaginosis in HIV-1 positive women and have enhanced growth in infants with congenital HIV-1 infection. Probiotic bacteria may stabilize CD4+ T cell numbers in HIV-1 infected children and are likely to have protective effects against inflammation and chronic immune activation of the gastrointestinal immune system.

Aims: Documentation of clinical-pathological features of 37 infants/children whose parents alleged a relationship between vaccination and death or permanent central nervous system (CNS) damage, and sought compensation through the National Vaccine Injury Compensation Program., Scope: Of the 5545 claims filed during the 10-year period (1990-1999), CNS tissue was available for evaluation by a pediatric neuropathologist in 37; 33 died and 4 had a biopsy or lobectomy. Most commonly implicated vaccines were DTP/DTaP, followed by MMR and IPV/OPV, but almost all of the vaccines currently given to infants/children were alleged to be responsible for the illness/death. No lesions were found in 5 of 37 (13.5%). The most frequent abnormality consisted of acute anoxic encephalopathy (14 of 37 - 37.8%), consequent to several different causes, such as positional asphyxia, cardio-respiratory arrest during status epilepticus, etc. The remaining children manifested other lesions, including inflammation (5 of 37 - 13.5%), vascular and developmental anomalies (4 each of 37 or 10.6%), cerebral edema and system degeneration (2 each of 37 or 5.4%), and one case of heavy metal exposure in a child living near an abandoned mine (2.2%)., Conclusions: There was no obvious relationship between type of vaccine (or vaccines simultaneously administered) to time of onset of symptoms, nature of symptoms or the lesions found., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We reviewed Food and Drug Administration postmarketing reports of central nervous system (CNS) anticholinergic effects in association with oxybutynin. Taking domestic usage by age group into account, there is a disproportionately higher number of CNS adverse event cases reported in pediatric patients as compared with adult patients. CNS stimulation was prominent in the pediatric cases.

Objectives: To gain a better understanding of the capacity of psychostimulant medications to induce adverse psychiatric reactions and determine the frequency of such reactions, we analyzed postmarketing surveillance data and clinical trial data for drugs, either approved or under development, for the treatment of attention-deficit/hyperactivity disorder., Methods: The US Food and Drug Administration requested manufacturers of drugs approved for attention-deficit/hyperactivity disorder or with active clinical development programs for that indication to search their electronic clinical trial databases for cases of psychosis or mania using prespecified search terms. The manufacturers supplied descriptions of clinical trials, numbers of patients exposed to study drug, and duration of exposure to permit calculations of incidence rates. Independently, cases of psychosis or mania in children and adults for drugs used to treat attention-deficit/hyperactivity disorder from the Food and Drug Administration Adverse Event Reporting System safety database were analyzed. Manufacturers were asked to conduct similar analyses of their postmarketing surveillance databases., Results: We analyzed data from 49 randomized, controlled clinical trials in the pediatric development programs for these products. A total of 11 psychosis/mania adverse events occurred during 743 person-years of double-blind treatment with these drugs, and no comparable adverse events occurred in a total of 420 person-years of placebo exposure in the same trials. The rate per 100 person-years in the pooled active drug group was 1.48. The analysis of spontaneous postmarketing reports yielded >800 reports of adverse events related to psychosis or mania. In approximately 90% of the cases, there was no reported history of a similar psychiatric condition. Hallucinations involving visual and/or tactile sensations of insects, snakes, or worms were common in cases in children., Conclusions: Patients and physicians should be aware that psychosis or mania arising during drug treatment of attention-deficit/hyperactivity disorder may represent adverse drug reactions.

Purpose: Our objective was to examine the numbers and characteristics of US pediatric adverse events (AEs) reported to the Food and Drug Administration (FDA)'s adverse event reporting system (AERS) for 5 years following implementation of the Best Pharmaceuticals for Children Act (BPCA) in 2002., Methods: We analyzed reports in AERS received by FDA from January 1, 2003 to January 1, 2008 for overall numbers, age, gender, and seriousness of outcome in children and adults. Pediatric and adult age groups (<2, 2-10, 11-17, 18-50, and >50 years of age) were further evaluated for most frequently reported suspect drug classes and AEs., Results: Seventy-two percent of 815 267 crude count reports had specified age information. Six percent of the total reports with age information reported age <18 years. Numbers of AEs being reported for children have remained steady, while those for adults have increased. The proportion of serious AEs reported was similar for pediatrics as compared to adults. Frequently reported suspect drug classes noted in pediatric age groups that were not observed in adults included anticonvulsants, attention deficit hyperactivity disorder (ADHD), anti-acne, and respiratory medications., Conclusions: This overview highlights the need for strengthening the passive drug surveillance system from a pediatric perspective, as well as investing in more active surveillance systems. Drug safety initiatives to better capture risk information in order to balance the risk/benefit of drug use in children.

Objectives: The Food and Drug Administration Modernization Act provided for an additional 6-month period of marketing exclusivity to companies that perform pediatric drug trials in response to a Food and Drug Administration-issued written request. Because many safety concerns cannot be detected until after the introduction of a product to a larger and more diverse market, the Best Pharmaceuticals for Children Act required the Food and Drug Administration to report to the Pediatric Advisory Committee on adverse events occurring during the 1-year period after granting pediatric exclusivity. We sought to describe the Pediatric Advisory Committee's recommendations made in response to safety reviews informed by data from the Food and Drug Administration Adverse Event Reporting System in 67 drugs granted exclusivity., Patients and Methods: Pediatric Advisory Committee meetings and data presented by the Food and Drug Administration for all drugs were reviewed from June 2003 through April 2007. We divided the drugs into 2 groups: those that were returned to routine adverse event monitoring and those that had specific Pediatric Advisory Committee recommendations., Results: Forty-four (65.7%) drugs were returned to routine monitoring for adverse events. The Pediatric Advisory Committee, sometimes working with other advisory committees, recommended label changes for 12 (17.9%) drugs, continued monitoring for 10 (14.9%), production of MedGuides for 9 (13.4%), and an update on label changes resulting from discussions with the sponsor for 1 (1.5%) drug. Some drugs had >1 action. Several of the adverse events revealed during this process were rare and life-threatening., Conclusions: Safety monitoring during the early postmarketing period is crucial to detect rare, serious, or pediatric-specific adverse events. Fortunately, the majority of drugs given exclusivity had no adverse events of a frequency or severity that prevented a return to routine adverse event monitoring.

The Division of Antiviral Drug Products of the US FDA has regulatory authority over the investigational new drugs under development by various sponsors to treat HIV-infected populations. The FDA and the sponsors of investigational new drugs use the Code of Federal Regulations to guide the entire drug development process, in order to ensure that safe and efficacious drugs are brought to market. To achieve this goal, diligent monitoring for safety during the pre-approval phase of new drug development is particularly crucial. When deciding what adverse experiences on clinical trials should be expeditiously reported, the Division recommends a conservative interpretation of the Code of Federal Regulations, where an adverse experience in a clinical trial of advanced HIV-infected patients is considered to be 'associated with the use of the drug' when the relationship cannot be ruled out with objective evidence. Fatal adverse experiences for subjects on clinical trials should be especially scrutinised. Safety reporting should be expedited when death occurs during clinical trials of advanced HIV-infected populations. The three components of an expedited reportable death occurrence, namely 'serious', 'unexpected' and 'associated with the drug use' as they relate to advanced HIV-infected populations, are discussed in this article. An occurrence of death is by definition serious. Unexpected experiences are unlisted adverse experiences, but need to be put into the context of specificity and severity. 'Associated with the drug use' has been clarified as 'relationship to the drug cannot be ruled out'. Because death in the advanced HIV-infected/AIDS population is usually a complex event, the possible contribution of the study drug is difficult to rule out. Thus, if the three components of the reporting requirement are met or insufficient information is available to make a firm determination of causality by the seventh day of the reporting period, the Division of Antiviral Drug Products expects expedited death reports on subjects participating in investigational new drug clinical studies.

There is marked activation of the endothelium and immune system in Kawasaki disease. Anticardiolipin antibodies (aCL) can cause activation of the endothelium. We measured aCL levels in acute Kawasaki disease patients and compared them to other febrile patients to see whether their aCL responses were different. Twenty-one patients with acute Kawasaki disease and 16 patients with an acute febrile illness were recruited. The aCL levels were measured in the sera of febrile patients and in Kawasaki disease patients prior to immunoglobulin therapy. There was no significant difference between the IgG aCL levels (p = 0.87) between the Kawasaki disease and febrile patients. However, the IgM (p = 0.01) and IgA (p = 0.03) aCL were significantly higher in patients with acute Kawasaki disease than in febrile children. Elevation of IgA aCL has been reported in association with other vasculitides and IgA-secreting plasma cells have been demonstrated in the vascular tissue in Kawasaki disease., (Copyright 2002 S. Karger AG, Basel)

Intravenous immune gamma-globulin (IVIG) is used successfully in the treatment of Kawasaki disease, with dose-dependent rapid resolution of symptoms such as fever and irritability and a decrease in ESR, WBCs, and platelets. The mode of action of IVIG in reducing this inflammatory response is not clearly understood. Recently anticytokine antibodies in IVIG have been demonstrated. Serum levels of proinflammatory cytokines have been shown to be elevated in patients with Kawasaki disease. The cytokine interleukin-6 (IL-6) is involved in the de novo production of acute-phase proteins by hepatocytes and cause thrombocytosis and fever in response to tissue injury. Patients receiving parenteral recombinant human IL-6 have dose-dependently experienced fever, malaise, chills, and acute-phase reaction. With high IL-6 concentrations, central nervous system toxicity has also been reported and IL-6 has been thought to mediate endothelial damage. We evaluated the response of stimulated blood cells of 12 normal children to IVIG in the release of the cytokines IL-6, IL-8, TNF-alpha. and IL-6 receptor (sIL-6R). The levels of cytokines IL-6, IL-8, and TNF-alpha (but not sIL-6R) in peripheral blood induced by stimulation with LPS were markedly reduced (P < 0.008) within 3 hr when incubated with IVIG compared to without IVIG. Thus we demonstrated that cells of normal children respond to IVIG in vitro by reducing cytokines such as IL-8, TNF-alpha, and IL-6 without affecting the level of receptor sIL-6R during an acute inflammatory response. We also found significantly higher IL-6 levels in children with Kawasaki disease compared to children with blood culture-negative febrile illnesses. In five children with Kawasaki disease we measured serum IL-6 before and after IVIG and assessed the clinical response to IVIG therapy. Therapy with IVIG was followed by a rapid resolution of symptoms in Kawasaki disease, with a significant decrease in serum IL-6. The attenuation of proinflammatory cytokine responses, especially IL-6, following infusions of IVIG may play an integral role in the rapid resolution of symptoms and decrease in the acute-phase proteins in children with Kawasaki disease. Cells of normal children were found to respond to the IVIG in a manner similar to that of the Kawasaki children.

The coexistence of congenital HIV infection with primary rheumatologic disease is rare. We have described a child with congenital AIDS and concurrent systemic lupus erythematosus who presented with small vessel vasculitis with no renal involvement. Oral corticosteroid therapy resulted in significant improvement in her clinical state. The child also responded strongly to potent antiretroviral therapy both virologically and immunologically.

Current evidence supports the concept that oral administration of probiotic lactobacilli may be therapeutic in preventing antibiotic-associated diarrhea in children and in reestablishing normal flora in the gastrointestinal tract. Children with human immunodeficiency virus (HIV) infections may have episodes of diarrhea and frequently experience malabsorption associated with possible bacterial overgrowth; together these may interact to produce the growth abnormalities characteristic of this group. The overall objective of this investigation has been to determine whether oral administration of the probiotic Lactobacillus plantarum 299v could improve nutrient status and promote growth in children congenitally exposed to HIV. In addition, the possible beneficial effect of Lactobacillus plantarum 299v in modulating immune response was evaluated. In preliminary results described here, we report on the ability of Lactobacillus plantarum 299v to colonize children with HIV and to elicit specific systemic immune response after oral supplementation.

Background: Experience in adults has shown that combination therapy including HIV protease inhibitors (PI) can profoundly affect viral replication and slow progression of HIV-associated disease. Trials defining the influence of PI and combination therapies on long term outcome of HIV infection in children have not yet been completed. Experience with infants and children who were receiving routine care in an HIV specialty clinic was reviewed to characterize the effect of changes involving one, two or three antiretrovirals., Methods: Clinical and laboratory findings of children in whom antiretroviral therapy was changed were retrospectively reviewed. Successful response was defined as a reduction of viral load of at least 0.7 log10 RNA copies/ml lasting for at least 3 months. Differences in characteristics and the character of the response associated with successful and unsuccessful changes were analyzed., Results: Of the 72 changes in therapy that were made in 54 children, 29 resulted in a successful response. A change involving 3 antiretrovirals was more likely to produce a successful response than a change involving 1 agent (6 of 9 vs. 6 of 24; P < 0.04). Reduction of viral load by > 100-fold or to undetectable amounts occurred more frequently in children who responded to a regimen containing a PI than in children who responded to reverse transcriptase inhibitors (11 of 21 vs. 1 of 8; P=0.05). Furthermore successful responses associated with addition of a PI were associated with a greater reduction in viral load than those that involved reverse transcriptase inhibitors (1.63+/-0.60 vs. 0.99+/-0.12 log10; P=0.003)., Conclusions: This experience suggests that changing antiretroviral therapy in HIV-infected children to regimens containing three drugs is more likely to result in a successful virologic outcome than changes in therapy involving one drug. This experience further supports the conclusion that including a PI as part of an antiretroviral regimen is more likely to result in a greater reduction in viral load in children.

Based on the recognition that interleukin-6 (IL-6) is produced early in infection, IL-6 determinations have been used to identify infants with early onset bacterial sepsis. This study intended to assess the value of IL-6 in maternal, cord and infant peripheral blood as an index of sepsis, and examine the relationships of its values in mother and infants. The population consisted of 17 mother/infant pairs at high risk for neonatal infection. Eight of these infants had clinical signs of possible sepsis. Cord blood IL-6 levels in infants of mothers considered to be noninfected were lower than those born to women with chorioamnionitis. There was also a positive correlation between maternal and cord blood IL-6 values. There were no differences in maternal blood IL-6, whether they had infections or not. Also, peripheral infant blood obtained after birth did not differentiate between those born to women with or without chorioamnionitis, nor did it correlate with maternal blood IL-6 levels. Clinical symptoms of the infants did not correlate with either cord or peripheral blood IL-6 values. Although maternal prepartum treatment with antibiotics and/or steroids may influence their own and their infants' blood IL-6 levels, there is insufficient evidence to consider low infant blood IL-6 level a reliable predictor to rule out early newborn sepsis.

HIV disease in perinatally infected patients is now treated as a chronic illness of childhood. The effective use of highly active anti-retroviral therapy has contributed to the improvements in the prognosis of this illness. As this population matures, the issue of disclosure of diagnosis becomes more significant and part of their comprehensive medical care. The importance of disclosure relates directly to medication adherence, treatment compliance, sexual exploration, fears associated with premature death, and the child's developing autonomy. disclosure of HIV disease to an infected child poses complex issues, such as transmissibility, maternal guilt, more than one family member with the virus, and the potential for social stigma and isolation, among others. A change in perspectives is currently taking place regarding the process of disclosure, whereby it may be approached as a gradual discussion process over the life of the child. A method of gradual and partial disclosure to the child with consistent support by a multi-disciplinary team of providers has been a successful strategy for many children cared for at the New York Hospital-Cornell University Medical Center. Of 73 perinatally HIV-infected children who are 6 years of age or older, 41% have had complete disclosure and another 19% are partially disclosed. Continuous communication and negotiation among the members of the team, which includes the parents and caregivers, are vital to the gradual process leading to complete disclosure.

Objective: To describe the changes in the characteristics of human immunodeficiency virus (HIV)-related deaths in children with perinatally acquired infection., Methods: A retrospective review of all deaths that occurred in HIV-infected children managed at The New York Hospital-Program for Children with AIDS during a 7-year period from January, 1990, to December, 1996. Differences in the characteristics at death between 15 children who died in 1990 and 10 children who died in 1996 were analyzed., Results: Fifty-eight deaths in our cohort of HIV-infected children were identified during the 7-year period. The mean age at death was 4.43 years. Sixty-nine percent of children were black, 55% were male and 94% were receiving Medicaid. The mean weight/age Z score was -3.9 and the mean CD4 index was 0.067 with 65% having <50 CD4 cells/microl at the time of death (TOD). The most common organ/organ systems to be involved at the TOD were lung (78%) and central nervous system (61%). Mycobacterium avium complex (MAC) was the most common isolate at the TOD (26%) followed by Pneumocystis carinii (20%) and Pseudomonas aeruginosa (17%). The leading non-infectious cause of death was cardiac failure (9%). Comparison of the characteristics at the TOD between 1990 and 1996 revealed significant differences in mean age (2.1 vs. 9.2 years, P < 0.0001), mean CD4 count index (0.18 vs. 0.02, P < 0.03), mean number of organ/organ system involvement (3.9 vs. 5.9, P < 0.05), percent receiving antiretroviral therapy (33% vs. 70%, P < 0.02), mean number of years receiving antiretroviral therapy (0.88 vs. 3.86 years, P < 0.01), percent receiving P. carinii pneumonia prophylaxis (27% vs. 100%, P < 0.001), percent receiving MAC prophylaxis/therapy (0% vs. 100%, P < 0.0001), and cause of death from P. carinii pneumonia (53% vs. 0%, P < 0.01)., Conclusions: Compared with children who died in 1990, HIV-infected children who died in 1996 were significantly older, more lymphopenic and more likely to have a greater number of organ system involvements and to have received antiviral therapy and antimicrobial prophylaxis. In 1996 no child died of P. carinii pneumonia. In 1996 MAC and P. aeruginosa were the two most important opportunistic infections causing death. These changes in the characteristics at death will warrant review of resources used in treating these children and may be critical in advising parents and care givers about the prognosis of this chronic infection.

Levels of interleukin-2 (IL-2) in serum obtained from human immunodeficiency virus (HIV)-infected children at health maintenance visits were measured to characterize endogenous IL-2 responses and to examine the association between these responses and progression of immunosuppression. IL-2 was detectable (level >8.7 pg/mL) in the serum of 28 of 45 HIV-infected children; 42% (19 of 45) had serum IL-2 levels of >39 pg/mL. Children without evidence of immunosuppression (Centers for Disease Control and Prevention Pediatric HIV Classification Immunologic Category 1, n = 15) and children with severe immunosuppression (immunologic category 3, n = 20) had statistically significant lower serum IL-2 levels (mean +/- [SD], 134.4 +/- 227.3 pg/mL and 18.2 +/- 30.3 pg/mL, respectively) than those with moderate immunosuppression (mean +/- [SD], 450.5 +/- 311.8 pg/ml; immunologic category 2, n = 10) (P < .05, Wilcoxon rank sum test). In those children in whom immunosuppression was evident, decreasing serum IL-2 levels correlated with depletion of CD4+ lymphocytes (r = 0.74), whereas there was an inverse correlation between serum IL-2 levels and CD4+ lymphocyte counts (r = -0.47) in children with no or moderate immunosuppression.