Premature newborns are highly susceptible to severe bacterial infections. This is partially due to their immature innate immune system, characterized by decreased neutrophil and monocyte activity as well as by reduced concentrations of complement factors. However, additional mechanisms might be important for innate immunity and are still the subject of considerable debate. The importance of pattern recognition domains such as Toll-like receptors (TLR) has been fully acknowledged within the last few years. Therefore, we investigated age-related monocyte TLR4 expression and lipopolysaccharide-induced cytokine secretion from very low birth weight infants (VLBWI) and from newborns after wk 30 of gestation in comparison to healthy adults. In VLBWI, expression of TLR4 surface protein, detected by flow cytometry, and TLR4-specific mRNA, quantified by real time-PCR, were significantly reduced in comparison to mature infants and to adults. Reduced TLR4 expression was paralleled by significantly diminished ex vivo LPS stimulated IL-1␤, IL-6, and tumor necrosis factor-␣ secretion into whole blood. We conclude that, in VLBWI, the minimized expression of TLR4 contributes to the susceptibility of VLBWI to infections with Gram-negative bacteria due to the lack of cytokines to boost initial immune response. (Pediatr Res 58: 121-124, 2005) Abbreviations CB, cord blood LPS, lipopolysaccharide PAMP, pathogen-associated molecular pattern PB, peripheral blood PBMC, peripheral blood mononuclear cells TLR, Toll-like receptor TNF, tumor necrosis factor VLBWI, very low birth weight infants Bacterial infections are a major cause of neonatal morbidity (1,2), and premature newborns are highly susceptible to infections (3). This increased susceptibility appears to be related to immaturity of the immune system. Maturation of the immune system includes specific humoral and cellular responses as well as nonspecific innate immune mechanisms, such as factors of the complement system and phagocyte activity (3-5).Monocytes and macrophages play a central role in both specific and nonspecific immunity against bacterial, viral, and fungal infection. In VLBWI, a substantial decrease of fully functional phagocytes has recently been reported (6). The Toll protein has been identified as a receptor controlling dorsoventral polarization during embryonic development of Drosophila larvae and serves a defensive function (7). Structures homologous to Toll receptors were found in mammalian cells (8,9) and termed TLR. Within the last few years, 10 human TLR have been described and characterized as important sensors of the innate immune system (9,10). These TLR are phylogenetically conserved and are involved in recognition of microbial PAMP. TLR4 functions as the transmembrane component of the LPS receptor. In addition to LPS, the major glycolipid component of the outer membrane of Gram-negative bacteria, TLR4 recognizes saturated and unsaturated fatty acids such as lipoteichoic acids from Gram-positive bacteria, and heat-shock proteins (8 -10). Binding of these ...

Pre-term neonates are at high risk to develop early-onset sepsis which possibly is caused by an immature immune system. Monocytes play a pivotal role as professional phagocytic and antigen-presenting cells in the innate immunity. In the present study, we investigated in monocytes from cord blood the expression of human leukocyte antigen (HLA)-DR as a marker for antigen-presenting capability, the expression of the high-affinity receptor for IgG (FcgammaRI/CD64), and the capacity to phagocytize non-opsonized Escherichia coli. We compared 70 infants in three groups according to their gestational age (group I: 20 very low birth weight infants (VLBWI), 24-31 weeks of gestation; group II: 25 pre-term infants, 32-36 weeks of gestation, and group III: 25 term neonates). The expression of CD64 as well as the phagocytic capacity of monocytes from cord blood were highest in VLBWI (p < 0.05 and p < 0.01, respectively). In contrast, HLA-DR expression was significantly (p < 0.05) diminished in VLBWI, which possibly leads to a reduced antigen-presenting capacity. We conclude that monocytes have different functional properties during gestational aging, which perhaps participate in the high incidence of infections in VLBWI.

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Within 25 years, 13 girls and 5 boys between the ages of 9 to 20 years were treated for differentiated thyroid cancer (DTC) at our institution. In 67% of the cases the diagnosis was made at an advanced stage indicated by cervical lymphnode metastases, two children showed metastases of the lung. Except for one girl, all patients underwent a total thyroidectomy with various forms of lymph node dissections. All were treated post-surgically with radio-iodine (131I) and all patients received levothyroxine in suppressive doses. The complication rate was low (laryngeal nerve injury in only 3 cases and no permanent hypoparathyroidism) and after a follow-up period of 26 years all patients are alive and without disease. In the case of DTC in children and adolescents, a total thyroidectomy with an appropriate lymph node dissection is the best surgical management. Besides the rather high incidence of local and distant recurrence, particularly in this age group, the detection and treatment of the metastases with radio-iodine are significantly facilitated by this surgical procedure. Additionally it allows the use of serum thyroglobulin as a reliable indicator of recurrence. To prevent high complication rates, surgical treatment should be performed in centers with skilled and experienced endocrine surgeons.

Despite the increasing prevalence of cervicofacial lymphadenitis due to atypical mycobacteria (AMB) in children, the true nature of AMB infection in clinical practice is poorly understood. The purpose of our study was to define the most common signs and symptoms, and to establish a workable scheme of diagnosis and treatment. Patients fulfilling the criteria of AMB infection (i.e., clinical signs, positive cultures or polymerase chain reaction, histologic features) were included in the study. All children underwent a standard surgical procedure, depending on pretreatment and the course of the disease. Sixteen infants presented with characteristic unilateral lymphadenopathy predominantly involving the submandibular area (13/16). Eight children had been initially treated at various institutions by fine-needle puncture or incision, and 7 of the 16 patients had received antituberculous multidrug treatment for a varying length of time. Complete excision of the affected lymph nodes was the definitive treatment in all patients. Three children had transient marginal mandibular nerve paralysis that resolved within a few months in all cases. Recognition of the characteristic features of AMB adenitis may permit early diagnosis and appropriate surgical treatment.