The role of adipokines in the pathogenesis and course of selected respiratory diseases

Adipose tissue is also a secretory organ producing active substances called adipokines. Some of them (apelin, resistin, adiponectin, leptin, chemerin, or visfatin) may play a role in the pathogenesis and course of respiratory diseases, e.g. COPD, asthma, pulmonary hypertension, or lung cancer. There are limited and conflicting data on the role of adipokines in asthma. It has been confirmed, however, that visfatin and leptin can be markers of inflammation in COPD. Elevated concentrations of leptin and resistin play a pro-inflammatory role in the development of cancer cachexia. The role of adipokines has also been demonstrated in pulmonary hypertension, and the apelinadiponectin axis disruption may exacerbate pulmonary hypertension

Cytokine Production by Peripheral Blood CD4+ and CD8+ T Cells in Atopic Childhood Asthma

There are conflicting studies on T cell cytokine production in childhood asthma. In this study intracellular cytokine expression of IL-2, IL-4, IL-10, IL-13, IFN-γ, and TNF-α in CD4+ and CD8+ T cells in children with atopic asthma were measured by flow cytometry. Results. A significant increase in the percentage of CD4+ and CD8+ T cells producing IL-4 and IL-13 and decrease in the percentage of CD4+ producing IFN-γ in asthmatic children was found. The percentage of CD4+/IL-13+ was significantly higher in severe asthma than in children with intermittent disease symptoms. Severity of asthma was associated with increased both serum IgE and frequencies of CD4+/IL-13+ T cells, as well as duration of disease. Moreover, a decrease in FEV1, FEV1/FVC was observed in relation to the severity of asthma. Changes in cytokine profile in CD8+ subpopulation didn't depend on the severity of the disease. Conclusions. Increased production of IL-4 and IL-13 in both CD4+ and CD8+ T cells accompanied by decreased IFN-γ expression in CD4+ T cells may be evidence that both lymphocyte subpopulations are implicated in the pathogenesis of asthma. Relationship of CD4+/IL-13+ T cells with disease activity suggests that this lymphocyte subset may have a prominent role in childhood asthma

Ocena stężenia adipokin u dzieci z mukowiscydozą

Introduction: Patients with CF present numerous pathological conditions such as malnutrition, depletion of fat-free mass, metabolic disturbances (abnormal glucose metabolism, increased insulin resistance, chronic energy deficit, local and chronic inflammation), which could affect or be associated with altered adipokines concentration Material and Methods: We aimed in this study to investigate the levels of selected adipokines such as resistin, apelin, adiponectin to demonstrate their application as possible markers of inflammation. Results: Serum level of resistin was higher (p < 0.001) and adiponectin - lower (p=0.02) in CF children than in healthy children. There was no difference in serum apelin level between two examined groups. However, values of adiponectin/BMI and apelin/BMI ratios in CF did not differ significantly from controls. Higher values of resistin/BMI ratio in CF in comparison to controls were observed Serum resistin/adiponectin ratio was significantly higher in CF patients than in controls (p < 0.0001). Resistin/BMI ratio correlated negatively with FEV1 (R:-48,p < 0.043). Serum resistin/adiponectin ratio correlated negatively with FEV1/FVC (R:-49, p=0.04), Adipokines showed no correlation with BMI and BMI-SDS, glucose, total cholesterol, and LDL-, HDL-cholesterol, triglyceride serum levels. Spirometric parameters FEV1, FVC, VC correlated negatively with serum glucose levels (R: -0.55, p < 0.018; R: -0.65 p < 0.0025; R:-0.76, p < 0.0008 respectively). FEV1 and FVC correlated positively with BMI-SDS (R:0.58, p < 0.01; R:0.5, p < 0.036, respectively). Conclusions: A significant increase in resistin concentration expressed also as resistin/BMI, and resistin/adiponectin ratios, observed in children with CF may suggests that this adipokine is involved in the inflammatory process underlying the disease and is related to worse spirometric parameters describing airways obstruction.Wstęp: Pacjenci z mukowiscydozą (CF) ujawniają liczne stany patologiczne, takie jak niedożywienie, zmniejszenie beztłuszczowej masy ciała, zaburzenia metaboliczne m.in. nieprawidłowy metabolizm glukozy, zwiększoną insulinooporność, przewlekły deficyt energetyczny, miejscowe i przewlekłe stany zapalne, które mogą wpływać lub być związane ze zmianami stężenia adipokin. Materiał i metody: Celem aktualnego badania było oznaczenie stężenia wybranych adipokin, takich jak rezystyna, apelina, adiponektyna w celu wykazania możliwości ich zastosowania jako markerów stanu zapalnego. Wyniki: Stężenie rezystyny w surowicy było wyższe (p &lt; 0.001) a adiponektyny — niższe (p = 0,02) u dzieci z CF niż u zdrowych dzieci. Nie stwierdzono różnicy w stężeniu apeliny w surowicy krwi pomiędzy tymi dwoma badanymi grupami. Wartości wskaźników adiponektyna/BMI i apelina/BMI u dzieci z CF nie różniły się jednakże znacząco od stwierdzanych w grupie kontrolnej. Obserwowano wyższe wartości wskaźnika rezystyna/BMI w CF w porównaniu z grupą kontrolną Wskaźnik rezystyna/adiponektyna w surowicy był znacząco wyższy u pacjentów z CF niż u osób z grupy kontrolnej (p &lt; 0.0001). Stosunek rezystyna/BMI korelował negatywnie z FEV1 (R: –48, p &lt; 0.043). Stosunek rezystyna/adiponektyna w surowicy korelował negatywnie z FEV1 / FVC (R: –49, p = 0,04). Stężenie adipokin w surowicy nie wykazało korelacji z BMI i BMI-SDS, stężeniem glukozy, cholesterolu całkowitego, stężeniem cholesterolu LDL i HDL, stężeniem triglicerydów. Parametry spirometryczne FEV1, FVC, VC korelowały negatywnie ze stężeniem glukozy w surowicy (R: –0,55, p &lt; 0.018, R: –0,65 p &lt; 0.0025, R: –0,76, p &lt; 0.0008). FEV1 i FVC wykazywały dodatnią korelację z BMI-SDS (R: 0,58, p &lt; 0,01, R: 0,5, p &lt; 0.036). Wnioski: Znaczne zwiększenie stężenia rezystyny wyrażone również jako wskaźnik rezystyna /BMI oraz stosunek rezystyna/adi­ponektyna, obserwowane u dzieci z CF może sugerować, że ta adipokina jest zaangażowana w proces zapalny leżący u podstaw choroby i jest związana z pogorszeniem parametrów spirometrycznych opisujących niedrożność dróg oddechowych

Is adiponectin in children with immunoglobulin A vasculitis a suitable biomarker of nephritis in the course of the disease?

Introduction: Immunoglobulin A vasculitis (IgAV) is the most common form of vasculitis in children. Nephritis in the course of this disease (IgAVN) is observed in 30–50% of patients and might lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Finding a non-invasive biomarker to distinguish initially between patients with and without nephritis and to facilitate a therapeutic decision to reduce the risk of long-term renal impairment is currently the target of much research. The aim of this study was to evaluate the adiponectin concentration in children with IgAV and estimate whether it might be used as a marker of IgAVN. Material and methods: The study involved 29 IgAV children and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). The serum adiponectin level was estimated in children in an acute phase of IgAV and after 2–6 months during a follow-up visit. The relationship between the concentration of adiponectin and anthropometric measurements, epidemiological data and laboratory parameters were evaluated. Results: The concentration of adiponectin in serum was significantly higher in children with acute phase of IgAV as compared to the control group (p &lt; 0.001), and in patients without renal involvement in comparison with IgAV-N children (p &lt; 0.049). In analysis of correlation we found a negative relationship between adiponectin level and serum creatinine concentration (r = –0.437, p = 0.02). The logistic regression evaluation demonstrated that a low adiponectin level increased the risk of nephritis in the course of IgAV. Conclusions: Our study revealed that the serum adiponectin level increased markedly in patients with IgAV. We also documented that higher risk of nephritis in the course of the disease was associated with lower concentration of this hormone

Ocena stężenia adypocytokin u dzieci z przewlekłą chorobą nerek

Introduction: Adipose tissue through the many secreted adipocytokines creates a highly active metabolic and endocrine organ. The evaluationof serum adipocytokine concentration in children with chronic kidney disease (CKD) could serve as a marker of cardio-vascularcomplication progression and an index of outcome in adulthood and after kidney transplantation.Material and methods: The aim of the study was to evaluate simultaneously the serum concentrations of six different adipocytokines:adiponectin, apelin, chemerin, omentin, resistin, and vaspin, in 28 children with CKD stage 5 on haemodialysis and peritoneal dialysis.Results: The concentration of apelin, omentin, and resistin in children with CKD was significantly higher and the concentration ofvaspin, adiponectin, and chemerin was significantly lower than in the control group. After adjusting to body mass index (BMI), the sameresults were obtained. After adjusting to body surface area (BSA), the concentration of vaspin, adiponectin, and chemerin did not differbetween children with CKD and the control group. In analysis of the correlation between serum total adipocytokine levels in childrenwith CKD we found a negative relationship in pairs: omentin–apelin and omentin–vaspin, and positive in pairs: adiponectin–chemerinand adiponectin–resistin.Conclusions: Our results show that changes in serum adipocytokines concentration are associated with the kidney dysfunction in CKDin children. Longitudinal studies on larger groups of paediatric cohorts would be helpful in investigating whether adipocytokines playa harmful role in the development of CKD and would enable further understanding of the risk factors for CKD progression.(Endokrynol Pol 2015; 66 (2): 100–107)Wstęp: Tkanka tłuszczowa poprzez wydzielane liczne adipocytokiny tworzy narząd bardzo aktywny metabolicznie i hormonalnie. Ocena stężenia adipocytokin w surowicy krwi u dzieci z przewlekłą chorobą nerek (CKD) może służyć jako marker progresji powikłań sercowo-naczyniowych i wskaźnik rokowniczy w wieku dorosłym i po przeszczepie nerki.Materiał i metody: Celem pracy była ocena stężenia w surowicy krwi jednocześnie sześciu różnych adipocytokin: adiponektyny, apeliny, chemeryny, omentyny, rezystyny i waspiny u 28 dzieci z CKD w stadium 5. leczonych hemodializami i dializą otrzewnową.Wyniki: Stężenie apeliny, omentyny i rezystyny u dzieci z CKD było znacząco wyższe, stężenie waspiny adiponektyny, chemeryny było znacząco niższe niż w grupie kontrolnej. Po skorygowaniu do wartości BMI uzyskano takie same wyniki. Po skorygowaniu do wartości powierzchni ciała stężenia waspiny, adiponektyny i chemeryny nie różniły się u dzieci z CKD i w grupie kontrolnej. W analizie korelacji pomiędzy całkowitym stężeniem adipocytokin w surowicy krwi u dzieci z CKD stwierdzono ujemną zależność w parach: omentyna–apelina i omentyna–waspina i pozytywną w parach: adiponektyna–chemeryna, rezystyna–adiponektyna.Wnioski: Wyniki przedstawionego badania wskazują, że zmiany stężenia adipocytokin w surowicy krwi są związane z upośledzeniem czynności nerek w CKD u dzieci. Długoterminowe badania w większych grupach pediatrycznych byłyby pomocne w wyjaśnieniu, czy adipocytokiny odgrywają niekorzystną rolę w rozwoju CKD, oraz umożliwiłyby dalsze zrozumienie czynników ryzyka progresji CKD. (Endokrynol Pol 2015; 66 (2): 100–107

Evaluation of the frequency of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T polymorphisms in adiponectin coding gene in girls with anorexia nervosa

Introduction: Anorexia nervosa (AN) is a serious chronic psychosomatic disorder, the essence of which are attempts by the sufferer to obtain a slim silhouette by deliberate weight loss (restrictive diet, strenuous physical exercise, provoking vomiting). The aetiology of this disorder is multifactorial. Genetic factors that influence the predisposition to AN have been sought. A broad meta-analysis points to a strong genetic correlation between AN and insulin resistance. Adiponectin (ADIPO) increases insulin sensitivity. In our pilot study we demonstrated that the TT genotype in locus ADIPOQ c.276 G&gt;T of the ADIPO gene and a higher concentration of ADIPO in blood serum occurred significantly more frequently in 68 girls suffering from AN than in 38 healthy girls. The objective of this study was to evaluate the frequency of the occurrence of ADIPOQ c.45 T&gt;G and ADIPOQ c.276 G&gt;T in the ADIPO gene in a larger cohort of girls with AN and healthy girls, as well as an analysis of correlations between variants of the aforementioned polymorphisms and the levels of ADIPO in blood serum. Material and methods: The study covered 472 girls (age: 11–19 years): 308 with the restrictive form of AN (AN) and 164 healthy girls (C). The level of ADIPO in blood serum was determined by means of the ELISA method on a Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in a ThermoCycle T100 thermocycler. 80–150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). Results: The distribution of genotypes in the polymorphic site ADP c.45 of the ADIPO gene and ADP c.276 was similar in both groups. In both groups the T allele was most frequent in locus ADIPOQ c.45 and the G allele in locus ADIPOQ c.276. In all the study subjects collectively (AN and C) a statistically significant negative correlation between the levels of ADIPO in blood serum on one hand and body weight (r = –0.46; p &lt; 0.0001) and BMI (r = –0.67; p &lt; 0.0001) on the other was demonstrated. Exclusively in the AN group a significant correlation between the level of ADIPO in blood and the distribution of TG, TT, and GG alleles in loci ADIPOQ c.45 and ADIPOQ c.276 was demonstrated (p = 0.0052 and p &lt; 0.0001, respectively). Conclusions: The genotype in loci ADIPOQ c.45 and ADIPOQ c.276 of the ADIPO gene seems to have no effect on the predisposition to AN. Girls suffering from AN with the TT genotype in loci ADIPOQ c.45 and ADIPOQ c. 276 may demonstrate higher insulin sensitivity because they have significantly higher levels of ADIPO than girls suffering from AN with other genotypes. This may be suggestive of their better adaptation to the state of malnutrition, and it has a potential effect on treatment results

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa

Introduction: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C&gt;G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G&gt;A and RETN c.-180C&gt;G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. Material and methods: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11–19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80–150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). Results: The average RES level in blood serum in the AN group was significantly lower (p &lt; 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p &lt; 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p &lt; 0.0001) and BMI (r = 0.61; p&lt; 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. Conclusions: The CG genotype in the locus RETN c.-180 C&gt;G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G&gt;A and RETN c.-180 C&gt;G of the resistin gene has no influence on the levels of this hormone in blood in AN patients

Bronchial asthma in obesity &#8212; a distinct phenotype of asthma?

Asthma and obesity have a considerable impact on public health and their prevalence has increased in recent years. Numerous large cross-sectional and prospective studies performed in adults, adolescents, and children throughout the world supports the hypothesis that obesity is an independent risk factor for asthma. The pathogenetic basis for asthma and obesity associations in humans is not well established. Obesity is capable of reducing pulmonary compliance, lung volumes, and the diameter of peripheral respiratory airways, and may influence on airway hyperresponsiveness. The increase of adipose tissue in obese subjects leads to a systemic inflammatory state, which produces a rise in the serum concentrations of several pro-inflammatory cytokines, chemokines and adipokines. The proinflammatory adipokines (leptin, resistin) and antiinflammatory (adiponectin) may be causally associated with asthma, however human studies are inconclusive. Obese asthma patients very often demonstrate increased asthma severity and relative corticosteroid resistance. Some studies suggest improvements in the disease with weight loss in obese asthma patients. Recently published data suggest that obese asthma patients may represent a distinct phenotype of asthma.Zarówno astma oskrzelowa, jak i otyłość, których częstość występowania wzrasta w ostatnich latach, stanowią istotny problem zdrowotny. Wyniki licznych badań przekrojowych i prospektywnych przeprowadzonych w grupie dorosłych osób, a także dzieci i młodzieży, wspierają hipotezę, że otyłość jest niezależnym czynnikiem ryzyka rozwoju astmy. Podstawy związków patogenetycznych astmy z otyłością nie są jednak dokładnie poznane. Otyłość może wpływać na zmniejszenie podatności płuc, objętości płucnych i średnicy obwodowych dróg oddechowych, a także na nadreaktywność oskrzeli. Zwiększenie ilości tkanki tłuszczowej u otyłych osób prowadzi do systemowego stanu zapalnego i zwiększenia stężenia w surowicy krwi wielu prozapalnych cytokin, chemokin i adipokin. Zarówno prozapalne adipokiny (np. leptyna, rezystyna), jak i przeciwzapalne adipokiny (np. adiponektyna) mogą mieć związek przyczynowy z astmą oskrzelową, ale wyniki badań na ten temat u ludzi są niejednoznaczne. U otyłych chorych na astmę oskrzelową często występuje cięższa postać choroby i częściowa oporność na inhalacyjne glikokortykoidy. Wyniki niektórych badań wskazują na poprawę kontroli astmy po redukcji masy ciała u otyłych chorych. Autorzy najnowszych publikacji sugerują, że astma u otyłych osób może stanowić odrębny fenotyp