Caesarean delivery has been linked to a number of inflammatory conditions in childhood and adolescence. Yet the mechanisms underlying these associations and their generalizability across contexts with different postnatal feeding and pathogenic exposures remain unclear. This study tests the association between delivery type and three measures of immune function, inflammation, morbidity and leukocyte proportions, in Ecuadorian infants and children aged 6 months to 2 years. Data were collected from mother–child pairs participating in a nationally representative health and nutrition survey Encuesta Nacional de Salud y Nutricion (ENSANUT-ECU) conducted in 2012. The analytic sample includes 828 mothers and infants with delivery information and measured biomarkers. Poisson regression models were used to examine the association between delivery type and markers of immune function, controlling for maternal and infant characteristics, including age, sex, sociodemographic characteristics and medical indications. 40.8% (n=338) of sample infants and children were delivered by caesarean. Compared to those born vaginally, infants born by caesarean were less likely to have elevated C-reactive protein (CRP) [CRP>2 mg/l; risk ratio (RR): 0.76, 95% confidence interval (CI): 0.58–1.00] and more likely to have illness symptoms (RR: 1.22, 95% CI: 1.01–1.46) and elevated basophils (RR: 1.83, 95% CI: 1.03–3.25). No other immune cell proportions differed by delivery type. The results suggest that differences in the perinatal exposures accompanying caesarean delivery may alter immune development and function, particularly in the inflammatory response to infection and in cells involved in the allergic response, across infancy and early childhood. Understanding the pathways linking perinatal exposures to immune development is important for preventing the development of inflammatory conditions.

Maternal obesity during pregnancy may influence fetal development and possibly predispose offspring to cardiovascular disease. The aim of the present study was to evaluate the relationship between maternal pre-pregnancy body mass index (BMI) and weight gain during pregnancy, and newborn birth weight, with lipid profile, high-sensitivity C-reactive protein (hs-CRP) and leukocyte in newborns. We performed a cross-sectional study of 245 mothers and their children. Blood was collected from the umbilical vein and assayed for lipid profile, hs-CRP and leukocyte count. Newborns average weight was 3241 g, total cholesterol 53.9 mg/dl, high-density lipoprotein cholesterol (HDL-c) 21.9 mg/dl, low-density lipoprotein cholesterol (LDL-c) 26.2 mg/dl, triglyceride 29.5 mg/dl and leukocytes 13,777/mm3. There was a direct correlation of pre-pregnancy BMI of overweight mothers with total cholesterol (r=0.220, P=0.037) and LDL-c (r=0.268, P=0.011) of newborns. Total cholesterol, LDL-c and HDL-c were higher in pre-term newborns (66.3±19.7, 35.9±14.6 and 25.2±7.7 mg/dl, respectively) that in full-term (52.4±13.1, 25.0±8.7 and 21.5±6.0 mg/dl), with P=0.001, 0.001 and 0.003, respectively. Leukocyte counts were higher in full-term newborns (14,268±3982/mm3) compared with pre-term (9792±2836/mm3, P<0.0001). There was a direct correlation between birth weight and leukocyte counts of newborns (r=0.282, P<0.0001). These results suggest the possible interaction of maternal weight and fetal growth with lipid metabolism and leukocyte count in the newborn, which may be linked to programming of the immune system.

Since decades, production traits such as growth rate, feed efficiency or body composition have been drastically increased in pigs by genetic selection. Whether this selection impacted animal robustness is still unclear. In this study, we compared Large White (LW) pigs, a breed submitted to intense genetic selection for production traits, and Basque (B) pigs, a local rustic breed, reared in two different housing environments (conventional v. enriched). Adaptation to housing conditions among each breed was evaluated at the level of endocrine and immune traits. These are known to be impacted by housing conditions and breed; however, the interaction effects between genotype and environment are less described. Animals (20 per breed and housing environment) entered the experiment at 35 kg of live weight. Levels of cortisol, acute-phase inflammatory proteins, immunoglobulins and hydrogen peroxide, blood formula, lymphocyte proliferation and in-vitro cytokine expression were measured at ∼115 kg of live weight. Animals were checked for skin injuries during the growing period. At slaughter, at the average live weight of 145 kg, carcasses were examined for pathological conditions of the respiratory tract. The major result was that the two breeds exhibited differences in response to the housing environment. Among the 24 sanitary, endocrine or immune traits investigated, the housing conditions affected eight variables in both breeds (salivary cortisol at 0700 and 1900 h, severity of pneumonia at slaughter) or only in B pigs (severe skin lesions) or LW pigs (salivary cortisol at 1500 h, granulocyte numbers and lymphocyte/granulocyte ratio and lymphocyte proliferation). These observations strengthen the hypothesis that selection for high meat production level might be associated with an increased susceptibility of animals to environmental stressors.

Genetic selection is well established as a means of improving productivity in pigs, but the effects of continued selection for increased performance on immunity are not well understood, nor are genetic relationships between performance and immunity. This study compared differences in the levels of a range of immune traits between lines of Large White pigs divergently selected for a number of productivity traits. Selection lines compared were high v. low lean growth under restricted feeding (31 high line v. 10 control v. 38 low line pigs), high v. low lean growth under ad libitum feeding (18 high line v. 10 control v. 19 low line pigs), and high v. low food intake (24 high line v. 26 low line pigs). Immune traits measured were total white blood cell numbers (WBC), and the numbers of leukocyte subsets: neutrophils, monocytes, eosinophils, lymphocytes, CD4+ cells, CD8α+ cells, B cells, γδ T cells and CD11R1+ Natural killer (NK) cells. CD4+, γδ T cells and CD11R1+ cells were subdivided into subpopulations that were positive or negative for the CD8α marker, and conventional CD8αhigh+ cytotoxic T cells were also determined. Pigs were tested under ad libitum feeding conditions from 14 to 24 weeks, and immune traits were assessed at ages 18 and 24 weeks. Line differences were estimated using residual maximum likelihood techniques. Consistent differences in immune trait levels were evident between pigs previously selected for high and low lean growth under restricted feeding: at age 24 weeks, high line pigs had higher basal levels of WBC (39·6 v. 27·8×106 cells per ml, s.e.d. 2·09, for high v. low line pigs) mainly explained by higher levels of lymphocytes (25·5 v. 17·3×106 cells per ml, s.e.d. 1·54, for high v. low line pigs) with increased numbers of CD8α+ cells (8·19 v. 5·15×106 cells per ml, s.e.d. 0·14) and CD11R1+ cells (5·23 v. 2·46×106 cells per ml, s.e.d. 0·43), predominantly the CD11R1+ CD8α? subpopulation ((3·20 v. 1·64×106 cells per ml, s.e.d. 0·11). High line pigs also had increased numbers of monocytes (2·64 v. 1·83×106 cells per ml, s.e.d. 0·35). Similar results were obtained at age 18 weeks. There were no consistent differences between divergent lines in pigs selected for lean growth under ad libitum feeding or food intake. This is the first report to demonstrate that selection for some aspects of performance can influence WBC and leukocyte subset numbers in pigs.

Background and objective: Volatile anaesthetic agents are known to influence neutrophil function. The aim was to determine the effect of chronic occupational exposure to volatile anaesthetic agents on the rate of neutrophil apoptosis among anaesthetists. To test this hypothesis, we compared the rate of neutrophil apoptosis in anaesthetists who had been chronically exposed to volatile anaesthetic agents with that in unexposed volunteers.

Methods: Venous blood (20 mL) was withdrawn from 24 ASA I-II volunteers, from which neutrophils were isolated, and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide.

Results: At 1 h (but not at 12 and 24 h) in culture, the rate of neutrophil apoptosis was significantly less in the anaesthetists – 13.8 (12.9%) versus 34.4 (12.1%) (P = 0.001).

Conclusions: Chronic occupational exposure to volatile anaesthetic agents may inhibit neutrophil apoptosis. This may have implications for anaesthetists and similarly exposed healthcare workers in terms of the adequacy of their inflammatory response.

Background and objective: Thiopental in clinically relevant concentrations inhibits the oxidative function of neutrophils, whereas only very high, non-therapeutic concentrations of methohexital induce a similar effect. The study characterized the molecular basis of this differential action of oxy- and thiobarbiturates on neutrophils.

Methods: Neutrophils were incubated in vitro with thiopental or methohexital using concentrations within the therapeutic range. Neutrophil responses were induced using different stimuli: N-formyl-L-methionyl-Lleucyl-L-phenylalanine (FMLP), C5a and 1,2-dioctanoyl-sn-glycerol (DiC8-DAG). FMLP and C5a bind to specific G-protein-coupled receptors that share the same second messenger cascade. In contrast, DiC8-DAG, an activator of protein kinase C, bypasses the signal transduction pathway downstream of the receptors. Hydrogen peroxide production by neutrophils was assessed using flow cytometry. To characterize the localization of the interaction site, FMLP receptor expression and cytosolic-free calcium were further analysed.

Results: FMLP and C5a-induced hydrogen peroxide production were both significantly impaired by thiopental, but not by methohexital. When postreceptor signalling was bypassed, by stimulation with DiC8-DAG, neither thiopental nor methohexital affected hydrogen peroxide production. Additionally, neither of the barbiturates impaired the cytosolic Ca2+ response.

Conclusions: We conclude that neither protein kinase C nor the hydrogen peroxide-generating enzymes are affected by thiopental or methohexital. The unimpaired Ca2+ response suggests that the function of the receptors and G-proteins were also unimpaired. Taken together, this indicates that the site of action of thiopental is in the cellular signalling upstream of protein kinase C.

Background and objective To investigate the ability of lidocaine to inhibit reactive oxygen and/or nitrogen species generation by either human leukocytes or cell-free systems via luminol- and lucigenin-enhanced chemiluminescence.

Methods Venous blood was obtained from healthy volunteers and leukocytes were isolated, from which chemiluminescence was generated. Also, chemiluminescence, induced by H2O2, HOCl, peroxynitrite or ferrous iron, was generated in cell-free systems.

Results Lidocaine produced a concentration-dependent inhibition in chemiluminescence generated by leukocytes (92 ± 1%, 1 mM). In cell-free experiments, lidocaine (1 mM) markedly inhibited chemiluminescence of xanthine-xanthine oxidase (24 ± 3%), while it slightly suppressed hypochlorous acid-induced chemiluminescence (9 ± 2%). Peroxynitrite-induced luminol- and lucigenin-enhanced chemiluminescence were also inhibited by lidocaine at 1 mM (19 ± 3% and 48 ± 8%, respectively). Lidocaine did not affect chemiluminescence generated by FeSO4. However, lidocaine produced a biphasic effect on H2O2-induced chemiluminescence (37 ± 5% inhibition at 0.01 mM and 61 ± 17% activation at 1 mM).

Conclusions Lidocaine can elicit direct scavenging activity at high concentrations that might be important at or near the site of injection in local anaesthetic use.

The effects of different anaesthetics on the neutrophil oxidative response in vitro are compared. Neutrophils were stimulated with small amounts of the bacterial peptide N-formyl-L-methionyl-L-leucyl-phenylalanine as a physiological, receptor-dependent stimulus. A new flow cytometry-based method capable of detecting the small amounts of H2O2 generated by neutrophils in a heterogenous all-or-none response following submaximal stimulation with N-formyl-L-methionyl-L-leucyl-phenylalanine was used. Propofol and thiopentone suppressed the respiratory burst significantly (P < 0.05 and P < 0.01) in therapeutic concentrations, while midazolam and methohexitone inhibited significantly (P < 0.01) only at concentrations greater than the therapeutic range. Impairment of the neutrophil response was primarily because of a reduction in the number of neutrophils participating in the respiratory burst and not of a proportional decrease of the fluorescence of all neutrophils.

The recruitment of leukocytes to the sites of inflammation and leukocyte-derived inflammatory mediators contributes to the development of tissue injury associated with inflammatory diseases. The first step in the pathogenesis of inflammatory conditions is adhesion of circulating leukocytes to activated vascular endothelial cell in the inflamed tissues and subsequent transmigration through the endothelial cells. During these processes, leukocytes are activated to secrete a variety of substances such as growth factors, chemokines and cytokines, complement components, proteases, nitric oxide, and reactive oxygen metabolites, which are considered to be one of the primary sources of the tissue injury. Prevention or reduction of leukocyte-endothelial cell adhesion often results in a profound attenuation of the microvasculature and parenchymal cell dysfunction in various animal models of human inflammatory diseases. It has been shown that all aspirin-like non-steroidal anti-inflammatory agents share at least one characteristic in that all of these agents diminish the adhesive interactions required for the accumulation of leukocytes at the site of inflamed tissue. The challenge for future investigations will need to be carefully examined: the relations between leukocyte and endothelial cell interactions, the mechanisms of activation of leukocytes and endothelial cells, and the components of the signaling pathways. Information related to these topics will allow a better understanding of the role of leukocytes in inflammatory tissue injury and the development of novel therapeutic strategies.