Fetal and neonatal IL-13 production during pregnancy and at birth and subsequent development of atopic symptoms

BACKGROUND: Cytokine production at the materno-fetal interface may influence the development of atopy-predisposing immune responses. Because IL-13 possesses IL-4-like activity and may regulate the immune responses observed in atopy, it may contribute to the expression of the atopic phenotype initiated during intrauterine life. OBJECTIVE: We sought to examine IL-13 expression by fetal and neonatal cells and the placenta. METHODS: The production of IL-13 by neonatal and fetal T cells was examined by culturing the cells in the presence or absence of PHA. Production of IL-13 at term was considered in the context of the later development of atopic disease in the child. IL-13 expression in the placenta was assessed by using immunohistochemistry. RESULTS: IL-13 immunoreactivity within the placenta was restricted to 16 to 27 weeks' gestation (6/6 positive vs 0/10 at >27 weeks' gestation). In contrast, spontaneous release of IL-13 by fetal mononuclear cells was first observed from 27 weeks' gestation but was undetectable after 37 weeks' gestation. PHA-stimulated mononuclear cells showed increased IL-13 levels in 80% of samples. Term babies (>37 weeks' gestation) with a parental history of atopy with atopic symptoms by 3 years of age produced significantly lower concentrations of PHA-induced IL-13 when compared with babies with no parental history of atopy (P =.034). CONCLUSION: Thus babies at risk of atopic disease in infancy display defective IL-13 production at birth. This may represent an inherent immaturity in the development of T cell-cytokine responses in babies at genetic risk for atopy or could be a consequence of downregulation of responses by other factors. Normal pregnancy, irrespective of atopic status, is associated with the production of appreciable quantities of IL-13 initially by the placenta and subsequently by the fetus. The regulation of this production and its consequences for the mother and fetus remains to be elaborated.     

The variable response of bacteria to free haemoglobin in the tissues

The local enhancement of infection by exogenous ferric iron, as ferric ammonium citrate, and by ferrous iron as guinea-pig haemoglobin, was assessed in studies with 55 strains of bacteria injected into the skin of guinea-pigs. The test organisms included Staphylococcus aureus, Streptococcus spp., Klebsiella spp., Escherichia coli and Pseudomonas aeruginosa. Four strains of Bacteroides spp. were tested with haemoglobin only. As previously reported with other strains, enhancement of infection by members of a given species by ferric iron was variable; in this study infection with only 11 of 59 strains was enhanced. Haemoglobin either of equal or lesser iron content was a more potent enhancer, affecting 27 of the 59 strains. The enhancement ranged from two-fold to 80-fold, the higher figures on the whole being characteristic of haemoglobin enhancement. Some few instances of depression by both haemoglobin and ferric ammonium citrate were noted. A few tests were made with systemic haemoglobin but the concentrations attainable were largely ineffective. Enhancement of infection did not appear to be related to the capacity of a strain to lyse or digest host red blood cells. In so far as guinea-pigs, whose antibacterial defences are lowered by ferric or ferrous iron, represent human subjects at risk of infection because of clinical circumstances characterised by excess of available iron--either exogenous or as a result of haemolysis--our results with organisms of a kind commonly associated with infection in hospitals suggest that only a small proportion of environmental bacteria can take advantage of any decreased resistance associated with iron excess.     

Immune function did not decline with aging in apparently healthy, well-nourished women

Nutrition plays a crucial role in immune function. Most studies on age-associated changes in immunocompetence in healthy adults did not examine the nutritional status of participants extensively. Inadequate nutritional status may confound the relationship of aging and immune response. The purpose of this study was to examine age-related changes in parameters of acquired and innate immunity in healthy and generally well-nourished older (62-88 years) versus younger (20-40 years) women. Subjects were screened for participation using the health criteria of the SENIEUR protocol as well as a number of nutrition criteria related to undernutrition, and protein, iron, vitamin B12, and folate status. Young and old women did not differ in total T (CD3+), T-helper (CD4+), or T-cytotoxic (CD8+) cell number. However, older women tended to have lower T-cell proliferation response to concanavalin A (P < 0.10) and significantly reduced response to phytohemagglutinin (P < 0.05). No age-related changes were noted in natural killer cell number or cytotoxicity. Phagocytosis and subsequent oxidative burst activity also did not differ between young and old women. Most immune parameters were not compromised with aging in this cohort of apparently healthy, well-nourished women. These findings highlight the importance of simultaneous examination of health and nutritional status in studies of immune function with aging.     

CD4 lymphocytes in the blood of HIV(+) individuals migrate rapidly to lymph nodes and bone marrow: support for homing theory of CD4 cell depletion

Recent studies have provided evidence that macrophages from Th1-prone mouse strains respond with an M1 profile, and macrophages from Th2-prone mouse strains respond with an M2 profile, characterized by the dominant production of NO or TGF-beta 1, respectively. We have shown that peritoneal macrophages from IL-12p40 gene knockout mice have a bias toward the M2 profile, spontaneously secreting large amounts of TGF-beta 1 and responding to rIFN-gamma with weak NO production. Moreover, IL-12p40KO macrophages are more permissive to Trypanosoma cruzi replication than their wild-type littermate cells. Prolonged incubation with rIL-12 fails to reverse the M2 polarization of IL-12p40KO macrophages. However, TGF-beta 1 is directly implicated in sustaining the M2 profile because its inhibition increases NO release from IL-12p40KO macrophages. IFN-gamma deficiency is apparently not the reason for TGF-beta 1 up-regulation, because rIFN-gamma KO macrophages produce normal amounts of this cytokine. These findings raise the possibility that IL-12 has a central role in driving macrophage polarization, regulating their intrinsic ability to respond against intracellular parasites.     

Familial translocation t(10;14) (q26.1;q32.3): report of three offspring with 10q deletion and 14q duplication

We describe two brothers and a cousin with common clinical features, including mild mental retardation, motor delays, hypotonia with truncal ataxia, esotropia, and mild facial and hand dysmorphia. The initial routine chromosome study failed to detect any abnormality in the proband. Based on a high index of clinical suspicion, high-resolution chromosome studies were performed on the proband's parents. A small reciprocal translocation t(10;14) (q26.1;q32.3) was detected in the father. The breakpoint on the derivative chromosome 14 was further placed telomeric to the immunoglobulin heavy-chain gene cluster at the band q32.33 by fluorescence in situ hybridization. Studies of the proband and two affected paternal cousins revealed that each had inherited the same derivative chromosome 10 from their carrier parents. This unbalanced karyotype resulted from an adjacent-1 segregation of the 10;14 translocation.     

Binding of influenza viruses to sialic acids: reassortant viruses with A/NWS/33 hemagglutinin bind to alpha2,8-linked sialic acid

We have examined the specificity of binding of A/NWS/33 hemagglutinin (HA), exploring the effects of fucosylation, changing the Gal-GlcNAc linkage between the second and third sugars, and binding affinity for alpha2,8-linked sialic acid. The HA of A/NWS/33(HA)-Tokyo/67(NA) (NWS-Tok, H1N2) virus binds to 3'-linked sialyllactose with 10-fold higher affinity than 3' sialyllactosamine and 3-fold higher affinity than 6' sialyllactosamine. The P227H mutation in A/NWS/33(P227H)(HA)-A/Memphis/31/98(NA) (NWS-Mem/98, H1N2) results in sevenfold lower affinity for 3' sialyllactose, but binding to 6' sialyllactosamine is unchanged. The apparent switch from 3' to 6' specificity is solely due to a loss of Siaalpha2,3 binding. Fucosylation of the third sugar and changing the linkage between second and third sugars had little effect on binding by NWS-Tok, but marked effects on A/NWS/33(P227H)(HA)-tern/Australia/G70c/75(NA) (NWS-G70c, H1N9) and NWS-Mem/98. NWS-Tok, NWS-G70c, and NWS-Mem/98 bind to alpha2,8-bisialic acid with high affinity. NWS-Mem/98 can also bind to alpha2,8-trisialic acid, but with lower affinity. Together, these data show that alpha2,8-linked sialic acid, fucosylation of the third sugar, and linkage between the second and third sugars could play important roles in allowing efficient virus binding to its host cell. The finding that influenza viruses have the potential to bind to alpha2,8-linked sialic acid is a new influenza virus-receptor interaction pathway.     

Extrapulmonary effects of maintenance therapy with theophylline and inhaled albuterol in patients with chronic asthma

The extrapulmonary effects of slow-release theophylline and an inhaled beta 2-agonist (albuterol) were examined separately and in combination among 18 adults and adolescents with asthma during a 3-month randomized, double-blind, crossover trial. Although neither global impressions nor daily diaries revealed differences in adverse effects, a structured questionnaire completed at the end of each regimen suggested a small but statistically significant increase in nausea and depressive and caffeine-like symptoms during the theophylline-containing regimens. Theophylline was also associated with improved verbal learning but decreased motor steadiness. Metabolic effects associated with theophylline included lower serum bicarbonate, greater urinary calcium excretion, and higher serum calcium, uric acid, and creatinine. Albuterol was associated with lower neutrophil counts and lower serum theophylline concentrations. There were no drug-induced effects on cardiac rhythm.