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Aims: The risk of neonates for severe infection/sepsis is reciprocally proportional to gestational age and birth weight. As monocytes and dendritic cells (DC) are recognised key antigen-presenting immune cells, we aimed to elucidate whether neonatal age is associated with reduced expression of human-leukocyte antigen-DR (HLA-DR) antigens on subsets of monocytes and DCs., Methods: Forty-three consecutive neonates (20 male, mean gestational age 236.0±26.8 days; mean 1-min Apgar score 7.5±2.0) were included in a monocentric prospective observational analysis. Patients were grouped according to gestational age (n=15 full-term, n=28 pre-term defined as <33 weeks). Ten healthy adult volunteers were assessed also. Flow-cytometric assessment of HLA-DR expression was performed in subsets of peripheral blood myeloid and plasmacytoid DCs (MDC and PDC) and monocytes (CD14brightCD16negative/CD14positiveCD16positive/CD14dimCD16positive). Clinical and routine laboratory data were followed up., Results: At birth, leukocyte counts were increased in full-term neonates. Monocyte counts were significantly increased in neonates when compared with adults (all P<0.05). A significant numerical increase of CD14brightCD16negative and CD14positiveCD16positive monocytes was noted in pre-term and full-term neonates (all P<0.05), while HLA-DR expression in these subsets was significantly diminished (most pronounced in pre-term infants, P<0.0001). MDC and PDC HLA-DR expression was reduced also (all P<0.05). Clinical indices (e.g., pH, days on antibiotics/mechanical ventilation, fever/sepsis) were not found to correlate with immunological indices., Conclusions: We observed a markedly diminished HLA-DR expression on monocyte and DC subsets in pre-term and full-term neonates, which may contribute to impaired antimicrobial defence mechanisms in the early days of life.

Background: As a protective response to an inflammatory stimulus, the antigen-presenting molecules (human leukocyte antigen-DR (HLA-DR)) on monocytes are downregulated. If severe, the response may lead to immunodepression or immunoparalysis, associated with an increased rate of morbidity and mortality in adults. In very low birth weight (VLBW) infants, birth and intensive care present major immunological challenges., Methods: We measured monocyte HLA-DR expression by flow cytometry and determined 13 plasma cytokines in 56 VLBW infants (gestational age (GA): 23.7-31.8 wk) and 25 controls (GA: 34.1-41.4 wk)., Results: HLA-DR expression decreased postnatally both in VLBW and in control infants. In VLBW infants, GA and respiratory distress syndrome (RDS) both showed associations with HLA-DR nadir on day 3, when 45% of them met the criteria of immunodepression. HLA-DR expression was lower in those infants subsequently developing infection (74 vs. 49% (day 3) and 85 vs. 68% (day 7); both P = 0.002). Interleukin (IL)-6 on day 1 was a predictor of the HLA-DR nadir., Conclusion: VLBW infants are in a state of immunodepression postnatally. This immunodepression correlated with GA and was a predisposing factor for late infections. The downregulation of HLA-DR during RDS probably indicates an RDS-induced antigen load on the immune system.

Respiratory distress syndrome (RDS) is a common problem and the leading cause of death in premature infants (PI). The introduction of surfactant treatment for RDS management has lowered mortality and morbidity; nevertheless, some neonates do not improve and are at increased risk of pulmonary hemorrhage. Inflammation, not only local but also systemic, seems to play an important role in the pathogenesis of RDS. To determine whether cytokine patterns characterize RDS and its outcome, we measured type-1 (IL-2, TNF-α, IFN-γ, IL-6) and type-2 (IL-4, IL-5, IL-10, TGF-β1) serum cytokines of 47 PI with established RDS and a control group of 30 healthy, appropriate for gestational age, full-term neonates. Cord blood samples were obtained at the time of delivery from PI and controls. Venous blood samples were collected from PI who received surfactant treatment and/or developed pulmonary hemorrhage. Significantly elevated cord blood cytokine levels were observed in PI at time of delivery, compared to controls, except for IL-5 and TNF-α levels that were within control range. The type-1/type-2 cytokine ratio was significantly increased in PI vs controls. Neonates who developed pulmonary hemorrhage between 2 and 3 days of life and/or died, presented the strongest Th1 and type-1 cytokine polarization that was mainly due to increased IFN-γ and TNF-α, and decreased TGF-β1. The majority of these PI were female with very low gestational age. Overall, PI with RDS present a Th1/type-1 cytokine polarization, which persists irrespective of the treatment provided, and is amplified when complications appear. Th1 polarization is associated with poor prognosis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Immaturity of the pulmonary and immune systems represents an important risk factor for increased morbidity and mortality in neonates. Surfactant protein (SP)-A and SP-D, linking molecules between these two systems, are critical for lung homeostasis as they regulate surfactant metabolism and host immunodefense activities in innate and adaptive immunity. Preterm neonates with respiratory distress syndrome showed lower concentrations of SP-A and SP-D, and the administration of exogenous surfactant was found to strengthen the secretion of SPs. Low levels of SP-A and SP-D also correlated with a higher risk of infection and development of bronchopulmonary dysplasia. Moreover, SP-A- and SP-D-enriched surfactant formulations were more resistant to the inhibitory action of the plasmatic proteins in animal models. Based on these assumptions, new-generation surfactants, enriched with SP-A and/or SP-D, may enhance the function of immune system and lungs in neonates, potentially improving the clinical outcome.

Objectives: Fetal lung maturation and respiratory outcomes are influenced by the exposure to intrauterine inflammation. Funisitis is considered as the histologic hallmark of fetal inflammatory response. This study was performed to determine if there is a difference in the rate of neonatal respiratory distress syndrome (RDS) according to the presence or absence of funisitis in preterm gestations., Study Design: The relationship between the presence of funisitis and the development of neonatal RDS was examined in 301 consecutive singleton preterm births (24-32 weeks' gestation). Cases without placental histological examination and those with major congenital anomalies were excluded. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton's jelly on the placental histological examination., Results: Funisitis was diagnosed in 25% and RDS was diagnosed in 46% of cases. The rate of RDS in babies with funisitis was lower than in those without funisitis (28.4% vs. 51.1%, p = 0.001). Logistic regression analysis demonstrated that the presence of funisitis was associated with a decreased risk for RDS after adjusting for confounding variables (Odds ratio = 0.44, 95% CI 0.22-0.90). The downward trend of the frequency of RDS was related to the presence of histologic chorioamnionitis and funisitis (p < 0.001)., Conclusions: The presence of funisitis is associated with a decreased risk for the development of neonatal RDS in preterm gestations. Furthermore, this observation suggests that the fetal involvement of placental inflammation may be beneficial to the maturation of the fetal lung., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Preterm infants with respiratory distress syndrome (RDS) present with systemic inflammation. The role of lymphocytes in RDS is less studied. Activation of lymphocytes could mediate chronic inflammation and development of bronchopulmonary dysplasia (BPD)., Objective: To evaluate whether T cells are activated in preterm infants with RDS and whether T cell activation is associated with the development of BPD., Methods: Thirty-four infants with RDS [mean gestational age 27.1 (SD 2.0) weeks, birth weight 900 (216) g] were compared with 21 infants without RDS [32.6 (1.4) weeks, 1,697 (406) g]. From blood samples taken on postnatal days 1, 3, and 7, CD4 and CD8 cell counts and their expressions of co-stimulatory molecule CD54 and adhesion molecule CD62L were determined by flow cytometry. In activated cells, expression of CD54 is increased and CD62L is decreased., Results: As compared with infants without RDS, infants with RDS had less CD4 and CD8 cells on day 3 (both p = 0.02). On day 1 and day 3, RDS was associated with increased CD54 expression on CD4 cells (p = 0.001; p = 0.03) and decreased CD62L expression on CD8 cells (both p = 0.02). Infants with RDS who developed BPD (n = 18) had higher CD54 expression on CD4 cells on day 3 (p = 0.01) and on CD8 cells on day 1 and day 3 (p = 0.01; p = 0.04) as compared with infants without BPD (n = 16)., Conclusions: In preterm infants, RDS is associated with a lower T cell count and a higher proportion of activated cells. Increased proportion of activated T cells predicts the development of BPD. Systemic T cell activation could mediate inflammation and development of BPD., (Copyright 2009 S. Karger AG, Basel.)

Aim: We investigated the role of eosinophils in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants., Methods: Fifteen preterm infants with BPD were compared to 13 preterms with respiratory distress syndrome (RDS) and to 16 healthy preterms. We assessed total eosinophil and neutrophil counts in venous blood samples and the levels of the eosinophilic activity markers eosinophilic cationic protein (ECP) and the cellular surface antigen (CD9)., Results: The eosinophil count was greater in BPD compared with RDS and healthy infants (1414 vs. 797 and 471 cells per microlitre, respectively, p = 0.03). ECP levels were elevated (34 vs. 12.8 and 9.8 microg/L, respectively, p = 0.002) and CD9 levels reduced (75 vs. 94 and 86 mean fluorescence intensity units, respectively, p = 0.01) in BPD compared with RDS and healthy infants, suggesting eosinophilic activation in BPD. These findings were not solely explained by differences between gestational age or birth weight of the different groups. ECP levels were positively correlated with the duration of oxygen supplementation in the BPD group. The eosinophil count fell promptly after steroid treatment was commenced in the BPD group., Conclusion: The findings suggest that BPD is linked to eosinophil activation, which might contribute to the pathogenesis.

Reactive oxygen species play an important role in the pathogenesis of respiratory distress syndrome and its complications. This study was conducted to determine if treatment with the antioxidant melatonin would influence interleukin-6, interleukin-8, tumor necrosis factor alpha, and nitrite/nitrate levels in newborns with grade III or IV respiratory distress syndrome (radiographically confirmed) diagnosed within the first 6 hours of life. Prior to treatment, a blood sample was collected from the umbilical cord or a peripheral vein of each newborn. Second, third, and fourth blood samples were collected at 24 hours, 72 hours, and 7 days, respectively, after beginning treatment with melatonin or placebo. Compared with the melatonin-treated respiratory distress syndrome newborns, in the untreated infants the concentrations of interleukin-6, interleukin-8, and tumor necrosis factor alpha were significantly higher at 24 hours, 72 hours, and at 7 days after onset of the study. in addition, nitrite/nitrate levels at all time points were higher in the untreated respiratory distress syndrome newborns than in the melatonin-treated babies. Following melatonin administration, nitrite/nitrate levels decreased significantly, whereas they remained high and increased further in the respiratory distress syndrome infants not given melatonin.

A key role for inflammation in the etiology of bronchopulmonary dysplasia (BPD) has been proposed. In the present study we have evaluated lymphocyte subpopulations in 39 premature infants with respiratory distress syndrome (RDS) who did or did not develop BPD. The absolute number of lymphocytes was lower among infants with RDS who developed BPD compared with those who did not over the first two weeks of life ( p < 0.020) as were percentage and absolute number of CD4(+) T cells. By contrast, the proportions of CD3(+)CD8(+) lymphocyte cells were not statistically different between non-BPD and BPD infants. B cell percentage was significantly decreased in BPD infants only on day 7. NK "bright" cells (CD56(+)) were highly enriched in all RDS groups. Interestingly, the percentage of CD4(+) T cells expressing CD62L was selectively reduced in BPD infants. As a whole these data suggest that reduction of CD4(+) T cells and especially those important in tissue migration and immune surveillance may be a factor in the pathogenesis of BPD.

Objective: To determine whether the presence of the proinflammatory cytokine interleukin (IL)-1beta in the lungs of preterm infants immediately after birth was associated with maternal inflammation and could predict adverse neonatal outcome., Study Design: Prospective evaluation of serially obtained tracheal aspirates for the presence of IL-1beta in 25 preterm infants (birth weight 595-1700 g; gestational age 24-32 weeks) with respiratory distress syndrome. The initial tracheal aspirate was obtained within 1 h after delivery., Results: An initial tracheal aspirate positive for IL-1beta had a highly significant correlation with documented maternal chorioamnionitis for the given patient. In addition, the presence of IL-1beta correlated significantly with elevated total cell count (2.62 vs. 0.96 x 10(6)/ml, p = 0.0097), granulocyte count (2.12 vs. 0.22 x 10(6)/ml, p = 0.001), macrophage count (0.28 vs. 0.01 x 10(6)/ml, p = 0.02) and the presence of proinflammatory cytokines IL-6, IL-8 and tumor necrosis factor (TNF)-alpha. Preterm neonates positive for IL-1beta in their initial sample were on prolonged assisted ventilation (38 vs. 16 days, p = 0.013) and oxygen supplementation (62 vs. 40.5 days, p = 0.0462) and required prolonged hospitalization (69 vs. 46 days, p = 0.0165)., Conclusions: The concentration of IL-1beta in the initial tracheal aspirate obtained from the lungs of preterm infants within the first hour of life may serve as a marker of antenatal/perinatal inflammation, probably due to maternal chorioamnionitis, and could predict an adverse clinical course and short-term outcome.

Unlabelled: The aim of this study was to investigate the effect of prematurity, neonatal sepsis, respiratory distress syndrome (RDS) and perinatal asphyxia on monocyte HLA-DR expression of neonates using a flow cytometric method based on monocyte negative selection. The subjects were one hundred and thirty-one neonates (59 healthy, 44 septicaemic, 20 with RDS and eight with perinatal asphyxia) and 20 healthy adults. Monocyte HLA-DR expression was measured using one-colour HLA-DR labelling in a gate for monocytes obtained using the combination of CD3-CD19--PE/CD15--FITC MoAbs. In addition, the common dual staining method using MoAbs against two CD14 epitopes (TUK4, MO2) was evaluated. With the one-colour HLA-DR labelling higher purity and recovery values of monocytes were achieved than with the dual labelling, Method: Healthy neonates had significantly lower percentages of HLA-DR(+) monocytes than adults (69 +/- 13% versus 91.5 +/- 2.5%) and comparable mean fluorescence intensity (MFI) (119 +/- 25 versus 131 +/- 26). Values did not differ significantly between healthy term and preterm neonates. Preterm neonates with RDS had a significantly lower percentage of HLA-DR(+) monocytes than the healthy preterm neonates. In neonates with asphyxia both parameters were comparable to those of the healthy ones. Septicaemic neonates presented significantly lower values of both parameters than the healthy, RDS and asphyxiated neonates. Monocyte negative selection provides a reliable estimation of HLA-DR expression on monocytes. Expression of monocyte HLA-DR is lower in healthy neonates in comparison with adults and is further decreased in neonates with sepsis and RDS, but it is not influenced by prematurity and perinatal asphyxia.

The influx of inflammatory mediators and cells into the tracheobronchial effluent of preterm infants with respiratory distress syndrome (RDS) appears to be important in signaling the development of bronchopulmonary dysplasia (BPD). The mechanism that initiates this early inflammatory response is not well understood. The purpose of this study was to test the hypothesis whether increased interleukin-8 (IL-8), a potent chemoattractant for human neutrophils, appears in the airways of preterm infants with RDS in whom BPD develops before the influx of neutrophils. In addition, airway secretions were analyzed for the cytokine interleukin-6 (IL-6) to test the hypothesis whether this pro-inflammatory cytokine is an early marker of inflammation in preterm infants with RDS who progress to BPD. Sixty-five infants less than 32 weeks gestation with RDS were enrolled on the first day of life and 56 infants completed the study, with 31 recovering from RDS (Non-BPD) and 25 infants progressing to BPD. Infants were excluded from enrollment in the presence of maternal chorioamnionitis, infection at birth, or infection within the first week of life. There were no significant differences in birthweight, gestational age, or prolonged rupture of membranes between the two groups. Serial tracheal aspirates (TA) were collected on days 1, 3, 5, and 7 while the infants remained intubated. Significant elevations of TA neutrophil counts were detected in the BPD group on days 5 and 7. Cell-free TA revealed marked elevations of IL-8 in the BPD group compared to the Non-BPD group [median (25th percentile, 75th percentile), ng/ml epithelial lining fluid (ELF)] on day 1 [BPD 485 (195, 840); Non-BPD 63.1 (28.3, 197), P < 0.05] and day 3 [BPD 740 (319, 1310); Non-BPD 111 (54.3, 337); P < 0.05], while on days 5 and 7, the differences were not statistically significant. Interleukin-6 (IL-6) was measured as a marker of acute inflammation and was not different in the two groups on day 1, but was significantly elevated on day 3 [median (25th percentile, 75th percentile), ng/ml ELF; BPD 297 (62.1, 702); Non-BPD 72 (32.8, 266), P < 0.05] and on day 5 [BPD 270 (136, 672); Non-BPD 86.4 (57.8, 138), P < 0.05]. These studies demonstrate that elevation of IL-8 and IL-6 levels precedes the marked neutrophil influx seen in the TA of preterm infants in whom BPD develop. The presence of IL-8 and IL-6 in TA from these infants suggests that these cytokines either initiate the acute inflammatory cascade in the lungs, or they are early markers of the inflammatory process that places preterm infants at high risk for BPD.

Intact phagocyte function is a pre-requisite for successful defence against infection, but paradoxically, these cells may also play a major role in the pathogenesis of the infant respiratory distress syndrome. Phagocyte function is known to be deficient in pre-term infants, who are at risk of infection as a result, but these infants are also at risk of respiratory distress syndrome as a result of surfactant deficiency. Despite this, few longitudinal studies of phagocyte function have been performed in pre-term infants. We have used lucigenin-enhanced chemiluminescence to examine the respiratory burst of mixed samples containing polymorphonuclear leucocytes and monocytes of 100 pre-term infants at 48- to 72-h intervals during their admission to a neonatal care unit. Increased polymorphonuclear leucocyte chemiluminescence was associated with respiratory distress syndrome and the use of intermittent positive pressure ventilation. Multiple linear regression analysis revealed a slight, but significant depression of chemiluminescence in association with the use of gentamicin and penicillin when stronger influencing factors such as the presence of respiratory distress syndrome were taken into consideration. Measurement of phagocyte function by sensitive luminescence assays requires very little blood and may be useful in pre-term infants to follow the severity of respiratory distress syndrome. However, it is probable that other factors such as antioxidant capacity also have an important influence on the degree of tissue damage.

Unlabelled: Premature children (n = 25) with respiratory distress (RD) were studied regarding complement activation and formation of the anaphylatoxins C3a and C5a. Blood samples were drawn on admission to the paediatric intensive care unit. In 18 of the patients RD was accompanied by other perinatal complications like pneumothorax or intracerebral haemorrhages. Seven of the premature children had RD without such complications. Preterm children with RD and with peri- and postnatal complications such as pneumothorax or intracerebral haemorrhage had increased concentrations in plasma of the anaphylatoxins C3a and C5a compared with preterm children with RD without these complications. There was a positive correlation between the plasma C3a and C5a concentrations in the preterm children., Conclusion: The present study indicates that isolated RD will appear without signs of complement activation and that complications like pneumothorax or intracerebral haemorrhages are associated with release of the anaphylatoxins C3a and C5a.

Preterm neonates are vulnerable to infection as a result of a compromised immune system. The function of neutrophils from 'well', 'stressed', and 'maturing' preterm neonates was compared with term neonate and adult neutrophils using a whole-blood phagocytosis assay. Cell surface expression of complement receptors and immunoglobulin G receptors was measured on neutrophils in whole blood from the same samples. Fewer actively phagocytosing neutrophils were found in all preterm neonate samples, especially in maturing neonates. Phagocytic rates were slower, and the number of Escherichia coli ingested was smaller in preterm neonate than in term neonate neutrophils. Expression of immunoglobulin G receptors and complement receptor 3 on neutrophils was not directly related to phagocytic activity.

Objective: Bronchopulmonary dysplasia (BPD) of preterm neonates is associated with an increased recruitment of inflammatory cells into the airways. To evaluate further the role of inflammation in the pathogenesis of BPD, tracheobronchial aspirate fluid of neonates with birth weight < 1200 g (n = 59) was sequentially analyzed in a prospective study., Methods: Tracheobronchial aspirate fluid was assessed for chemotactic activity, neutrophil cell count, concentrations of elastase-alpha 1-proteinase inhibitor and activity of free elastase, concentrations of chemoattractants (complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8), and albumin concentrations as well as alpha 1-proteinase inhibitor activity. The secretory component for immunoglobulin A was used as reference protein. Only specimens without evidence of microbiological colonization were studied., Results: In neonates with prolonged respiratory disease (BPD-risk neonates, n = 24, fraction of inspired oxygen > or = 0.3 and/or peak inspiratory pressure > or = 16 cm H2O at day 10 postnatal age, birth weight 892 +/- 36 g, gestational age 27.2 +/- 0.3 weeks) chemotactic activity, cell count, concentrations of the chemoattractants complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8, as well as levels of elastase-alpha 1-proteinase inhibitor were significantly higher at day 10 and/or day 15 of postnatal age compared with neonates without chronic pulmonary disease (total n = 35; day 10, n = 11; day 15, n = 8). There was no difference in free elastolytic activity. Concentrations of albumin as well as alpha 1-proteinase inhibitor activity were higher in BPD-risk patients on day 15, indicating an increased pulmonary leak., Conclusion: We conclude that preterm neonates at risk for the development of BPD show an enhanced inflammatory reaction in the lungs and an associated increase in pulmonary microvascular permeability. We speculate that inflammation may play an important role in the pathogenesis of BPD.

Serum from premature infants enrolled in either single-dose or multidose surfactant replacement studies with bovine lung-based exogenous surfactant (Survanta) were analyzed for antibodies reactive with mixtures of bovine surfactant proteins SP-B and SP-C. Sera from 404 premature infants enrolled in single-dose studies and 1024 premature infants enrolled in multidose studies were analyzed, representing a total of 987 samples and 2743 serum samples, respectively. The sera were obtained from treated and control infants at the time of treatment and 1 week, 4 weeks, and 6 months thereafter. Polyclonal antisera generated in rabbits against the small molecular weight proteins were uniformly reactive with the bovine surfactant test antigens; however, antibodies reacting with the surfactant proteins were never detected by immunoblot analysis with the infant sera. Antibodies against common human viral antigens were readily detected in infant serum samples. The horseradish-peroxidase conjugated second antibodies (antihuman immunoglobin G or antihuman immunoglobins A, G, and M) used in the studies were highly reactive with both immunoglobin G and immunoglobin M classes of human antibodies. Therefore there was failure to detect specific immunological responses to the bovine surfactant proteins present in Survanta after single or multiple doses of exogenous surfactant administered in the perinatal period.

The levels of CH50, the complement components, C1q, C4, and C3, C3 degradation fragments, and factor B were determined in the cord blood of 128 newborn infants. The levels of C3, C4, and C3d3 (an index of chronic in vivo complement activation) were clearly lower in the 28 infants with respiratory distress syndrome (RDS) than in the infants with other lung diseases or with normal lungs. CH50 and factor B levels were also low in RDS. Levels of C1q and other serum components in RDS infants were similar to the average levels in other infants without RDS at a corresponding gestational age. Lung surfactant is synthesized in alveolar type 2 cells, in which the complement components C4, C3, and factor B, but not C1q, have been reported to be synthesized. It seems possible that common factors regulate the synthesis of some complement components and surfactant.

In conclusion, we have shown that human surfactant is immunogenic and that circulating surfactant-antisurfactant immune complexes are detectable in the plasma from infants and in adults with RDS. We found these immune complexes regardless of whether exogenous surfactant was used in the individual treatment regimen. These immune complexes do not yet seem to cause disease in the short term. Long-term effects, if any, are unknown. Indications for surfactant replacement therapy in neonatal RDS are clear. Trials of exogenous surfactant are just beginning in adult RDS, and potential immunogenicity will be of even greater concern in these patients. In all such situations, potential for side effects must be balanced against therapeutic efficacy and the gravity of the disease. Our data indicate that surfactants, particularly heterologous surfactants, are potent immunogens. One cannot assume that using homologous or heterologous surfactants in patients with RDS will always be immunologically innocuous. Nonetheless, based on present data, moderately long-term follow-up (2 to 4 years), we are encouraged by our observation that no selective adverse effects attributable to human surfactant have been recognized, yet mortality from RDS in infants less than 30 weeks has been nearly cut in half.

The authors sought to determine whether treatment of respiratory distress syndrome (RDS) with human surfactant resulted in the formation of detectable circulating immune complexes. Preterm infants with severe RDS were divided into two groups: one group received human surfactant by intratracheal instillation and the other group did not. Both groups received ventilatory management involving intermittent mandatory ventilation. Plasma samples were drawn from these babies prior to treatment and at intervals thereafter. The authors developed an ELISA assay specific for surfactant-anti-surfactant immune complexes and analyzed the plasma samples for such immune complexes. Complement levels were also measured. They found that with time plasma from RDS infants in both groups showed evidence of surfactant-anti-surfactant immune complex formation. The concentrations of immune complexes generally peaked within the first week of life and then appeared to diminish over 1-4 weeks after birth in RDS infants. There was no evidence at any time in either group of immune-complex-mediated injury or of decreased serum complement levels. It is concluded that circulating immune complexes between surfactant and antibodies to surfactant are probably found in most neonates with respiratory distress syndrome, that they do not produce pulmonary damage detectable by clinical and serologic means, and that treatment of neonatal RDS with human surfactant similarly does not produce lung injury as determined with these techniques.