Kosti koje formiraju kostur u ljudskome tijelu ne služe samo za pokretanje i zaštitu unutarnjih organa, već obavljaju i specifične metaboličke procese od kojih je najbitniji metabolizam kalcija i ...fosfata. Bolesti u čijoj je patogenezi kronični upalni proces (prvenstveno je riječ o upalnim reumatskim bolestima poput reumatoidnog artritisa) mehanizmima na razini proupalnih stanica, proupalnih citokina i molekula dovode do povećanja broja osteoklasta koji su odgovorni za narušenu homeostazu metabolizma kosti, tj. povećanu resorpciju. Osteoimunologija je interdisciplinarna struka koja proučava povezanost osteologije i disregulacije imunosnog sustava i imunosnog odgovora. Saznanja dobivena proučavanjem osteoimunoloških mehanizama pomažu boljem razumijevanju gubitka koštane mase kod patoloških proupalnih stanja te omogućuju istraživanje novih lijekova koji bi mogli prekinuti taj proupalni proces.
Izhodišče: Diabetično retinopatijo lahko opredelimo kot kronično subklinično vnetje. Želeli smo ugotoviti razlike v ravneh vnetnih citokinov med steklovino in serumom pri bolnikih s proliferativno ...diabetično retinopatijo (PDR) pri kontrolni skupini ter primerjati ravni citokinov v steklovini glede na aktivnost PDR. Boljše poznavanje vnetnega dogajanja v očesu bolnikov s PDR bi lahko prispevalo k razvoju novih načinov zdravljenja teh bolnikov.Metode: V raziskavo smo vključili 37 bolnikov (37 oči) s PDR, pri katerih je bila potrebna vitrektomija, ter 20 bolnikov (20 oči) z idiopatskim foramnom makule (FM), ki so predstavljali kontrolno skupino. Glede na pregled pred operacijo in oceno očesnega ozadja med samim posegom smo opredelili aktivnost PDR. V steklovini in serumu smo s citometrično metodo CBA (angl. Cytometric Bead Array) analizirali citokine interlevkin 1β (IL-1β), dejavnik tumorske nekroze α (TNF-α), makrofagni vnetni protein 1α (MIP-1α), makrofagni vnetni protein 1β (MIP-1β), monocitni kemotaktični protein 1 (MCP-1), žilni endotelni rastni dejavnik (VEGF), interlevkin 6 (IL-6), interlevkin 8 (IL-8), interlevkin 10 (IL-10) in interlevkin 12 (IL-12).Rezultati: Ravni vseh citokinov so se v steklovini pomembno razlikovale od ravni v serumu. Raven MCP-1, VEGF, IL-6, IL-8 v steklovini bolnikov s PDR je bila statistično pomembno višja v primerjavi z ravnijo v steklovini pri bolnikih v kontrolni skupini, raven MIP-1α, IL-10 in IL-12 v steklovini bolnikov s PDR je bila statistično pomembno nižja v primerjavi z bolniki v kontrolni skupini (p < 0,05). Ravni citokinov v serumu bolnikov s PDR se niso pomembno razlikovale od ravni citokinov pri kontrolni skupini. Bolniki z aktivno PDR so imeli v steklovini višjo raven MCP-1, VEGF, IL-6 in IL-8 kot bolniki z inaktivno PDR, a razlike niso bile statistično značilne.Zaključek: Z našo analizo smo potrdili pomembne razlike v ravneh citokinov med steklovino in serumom pri bolnikih s PDR, kar kaže na pomen lokalnega vnetnega dogajanja v očesu pri PDR. Višje ravni MCP-1, VEGF, IL-6 in IL-8 nakazujejo aktivnost PDR.
Some of the universal characteristics of pre-agricultural hominin diets are strikingly different from the modern human diet. Hominin dietary choices were limited to wild plant and wild animal foods, ...while the modern diet includes more than 70 % of energy consumed from refined sugars, refined vegetable oils, and highly processed cereals and dairy products. The modern diet, with higher intake of fat has also resulted in a higher ratio of omega-6 (n-6) to omega-3 (n-3) polyunsaturated fatty acids (PUFA), contributing to low-grade chronic inflammation (LGCI) and thus promoting the development of many chronic diseases, including obesity and osteoporosis. In this review, we describe the changes in modern diet, focusing on the kind and amount of consumed fat; explain the shortcomings of the modern diet with regard to inflammatory processes; and delineate the reciprocity between adiposity and inflammatory processes, with inflammation being a common link between obesity and osteoporosis. We present the evidence that overconsumption of n-6 PUFA coupled with under-consumption of n-3 PUFA results in LGCI and, along with the increased presence of reactive oxygen species, leads to a shift in mesenchymal stem cells (precursors for both osteoblasts and adipocytes) lineage commitment toward increased adipogenesis and suppressed osteoblastogenesis. In turn, high n-6 to n-3 PUFA ratios in the modern diet, coupled with increased synthesis of pro-inflammatory cytokines due to adiposity, propagate obesity and osteoporosis by increasing or maintaining LGCI.
Pojedina univerzalna svojstva prehrane hominina prije pojave poljodjelstva izrazito se razlikuju od suvremene prehrane. Prehrambene navike hominina vjerojatno su bile ograničene na plodove divljeg bilja i lovinu; više od 70 % moderne prehrane odnosi se na konzumaciju rafiniranih šećera, biljnih ulja, žitarica i mliječnih prerađevina. Moderna je prehrana s višim unosom masti također dovela do nepovoljnijeg omjera omega-6 i omega-3 višestruko nezasićenih masnih kiselina (engl. krat. PUFA), koji pridonosi održavanju kronične upale niskoga stupnja, a time i nastanku mnogih kroničnih bolesti, uključujući pretilost i osteoporozu. U ovom se preglednom članku opisuju promjene uslijed modernog načina prehrane, s posebnim osvrtom na vrste i količine konzumirane masti. Također se objašnjavaju nedostatci moderne prehrane s obzirom na upalne procese te međusobna povezanost između pretilosti i upalnih procesa, koji su usto i poveznica između pretilosti i osteoporoze. U članku se iznose saznanja o tome da pretjerana konzumacija omega-6 masnih kiselina uz nedostatnu konzumaciju omega-3 masnih kiselina dovodi do kronične upale niskoga stupnja i povišenih vrijednosti reaktivnih kisikovih čestica (ROS), a time i do pomaka u mezenhimskih matičnih stanica (prekursora osteoblasta i adipocita) prema povećanoj adipogenezi i smanjenoj osteoblastogenezi. Uz povećanu sintezu upalnih citokina zbog pretilosti, moderna prehrana s nepovoljnim omjerom omega-6 i omega-3 kiselina u korist prvih nastavlja poticati pretilost i osteoporozu jer održava i pogoršava kroničnu upalu.
Eozinofilni ezofagitis je kronična bolest posredovana putem Th2 obrasca imunosne reakcije, karakterizirana prisutnošću predominatno eozinofilnih upalnih promjena u jednjaku. Bolest je posredovana ...imuno/antigenim patofizološkim putem, a za definiciju bolesti potrebno je prisustvo kliničkih simptoma i histoloških elemenata bolesti. Unatrag desetak godina bilježi se porast incidencije i prevalencije EoE, gdje prevalencija EoE varira, te u općoj populaciji iznosi 0,2–4/1000 u asimptomatskih bolesnika, dok kod simptomatskih bolesnika ona iznosi 5–6%. Smatra se da prevalencija u općoj populaciji iznosi 43 do 52/100000. Patofiziološki riječ je o poligenskoj bolesti u kojoj određeni citokini (IL-4, IL-5,IL-13, IL-14, TGF-β) igraju ključnu ulogu aktivirajući eotaksin-3 u sluznici jednjaka. Eotaksin-3 snažno privlači eozinofile u sluznicu jednjaka, a tako aktivirani eozinofili dovode do privlačenja drugih upalnih stanica, oslobađanja medijatora i nastanka bolesti. Histološki kriterij dijagnoze EoE je prisutnost više od 15 eozinofila prisutnih u vidnom polju bioptata sluznice jednjaka. Klinički, bolest se može manifestirati spektrom simptoma, od akutne impakcije hrane, disfagije, boli u žličici i žgaravice, a i nespecifični simptomi poput inapetencije ili povraćanja također se javljaju kod ovih bolesnika. Osnova liječenja ovih bolesnika temelji se na medikamentnom liječenju, dijetalnim preporukama i endoskopskoj dilataciji. Cilj ovih kliničkih smjernica jest prikazati preporučeni algoritam dijagnostike i liječenja eozinofilnog ezofagitisa.
Immunological alterations may led to the reduction in capacity and endurance levels in elite athletes by e.g. increased susceptibility to infections. There is a need to explain the impact of ...intensive physical effort on the CD4
memory T cell subsets.
Fourteen participants median aged 19 years old (range 17-21 years) were recruited form Pogoń Szczecin S.A., soccer club. They performed progressive efficiency test on mechanical treadmill until exhaustion twice: during preparatory phases to spring and autumn competition rounds. We examined the influence of exhaustive effort on the selected CD45
, especially CD4
memory T cell subsets and inflammation markers determined before, just after the test and during recovery time.
Significant changes in total CD45
cells and decrease in T lymphocytes percentage after the run was observed. Significant fluctuations in T cells' distribution were related not only to the changes in Th or Tc subsets but also to increase in naïve T cell percentage during recovery. Increase in TNF-α and IL-8 post-exercise, IL-6 and IL-10 plasma levels in recovery was also found.
The novel finding of our study is that the run performed on mechanical treadmill caused a significant release of CD4
T naïve cells into circulation. Post-exercise increase in circulating NK cells is related with fast biological response to maximal effort. However, at the same time an alternative mechanism enhancing inflammation is involved.
Acute pancreatitis (AP) is a common, potentially lethal, acute inflammatory process with a highly variable clinical course. The aim of this study was to analyse early changes in the serum ...concentrations of pro- and anti-inflammatory cytokines in the peripheral blood of patients with the interstitial form of acute pancreatitis (IAP) and necrotic acute pancreatitis (NAP), especially in those patients who had lethal outcomes.
The prospective study enrolled 52 patients who were divided into IAP (65.38% of patients) and NAP (34.62% of patients) groups. The serum levels of interleukins (IL) 6, 8 and 10, together with tumour necrosis factor (TNF)-alpha were measured on the 1
and 3
day of hospitalisation. Significantly higher values of IL-6, IL-8 and IL-10 were found on day 1 and 3 in NAP than in IAP. IL-6 was significantly higher on both days of measurement, whereas IL-10 on the first day and IL-8 on the third day were significantly higher in the group of patients who did not survive in comparison with patients who had the interstitial form of AP.
In conclusion, the data from this study showed that immune suppression and excessive immune stimulation in the first three days after admission could indicate the development of NAP and a potentially lethal outcome.
During karate fight muscles work at a very high intensity, and their contractions are extremely strong. The movement pattern contains a great number of feints, dodges, frequent changes in movements' ...tempo and direction, hits and kicks, all of which is highly stressful for athlete's organism, including the immune system.
T lymphocyte subsets' distribution and selected cytokines in peripheral blood of three elite karate athletes aged 30 years old (range 21-31 years) with minimum 15 years of training experience were analysed in two experiments: at the beginning of the preparatory phase (a progressive test until exhaustion; an analysis of immune system's selected parameters and cardiorespiratory fitness measures, including VO
max, VE, AT, MVV, MET, Rf), and during the start-up period (Karate Championships; an analysis of selected parameters of the immune system).
Maximal effort caused an increase in total lymphocyte percentage (p<0.05). A decrease in Th cells in recovery (p<0.05 compared to post-exercise), and an increase in Th naïve cells in recovery (p<0.05) were observed. A significant increase in CD8
central memory cells (p<0.05) was found only after the progressive test, and no changes in both central and effector memory subsets of CD4
cells during the first experiment. An increase (p<0.05) in Treg and Th1 and a decrease (p<0.05) in Th2 cells' distribution during recovery time were found. Additionally, changes (p<0.05) in TNF-α, IL-6, IL-8, IL-10 and IL-12p70 were observed.
Post-effort disorder in immune balance activated compensation pathways involving CD4
cells. Treg and Th1 cells seem to be subsets of key importance involved in the anabolic effect of physical effort, at least among karate athletes.
Host response to antigen stimulation in chronic inflammatory periapical lesions is mainly controlled by the balance between proinflammatory and anti-inflammatory cytokines. The aim of this study was ...to determine the concentration of TGF-β
in the tissue homogenates of periapical lesions and to analyse its level in relation to the symptomatology of the patients and size of the lesions. Ninety three samples of chronic periapical lesions were obtained after extraction of teeth. Samples were divided according to the clinical symptoms as symptomatic and asymptomatic, and according to the size as large and small. The concentration of TGF-β
was analyzed using ELISA. The results showed increased production of TGF-β
in symptomatic lesions compared to asymptomatic, but the difference was not statistically significant. Statistically significant difference in TGF-β
concentrations was observed in large lesions compared to small (p<0,001). It seems that TGF-β
have a modulating effect on bone tissue resorption activity under the influence of proinflammatory cytokines and can be molecular prognostic marker of periapical lesion healing.
Balans između proinflamatornih i antiinflamatornih citokina u velikoj meri kontroliše odgovore domaćina na antigenu stimulaciju kod hroničnih inflamatornih periapeksnih lezija. Cilj istraživanja bio je da se odredi koncentracija TGF-β
u homogenatima tkiva periapeksnih lezija i da se rezultati uporede u odnosu na simptomatologiju pacijenata i veličinu lezije. Ispitivano je 93 uzorka hroničnih periapeksnih lezija dobijenih nakon ekstrakcije zuba. Uzorci lezija su podeljeni prema simptomatologiji pacijenata na simptomatske i asimptomatske, a prema veličini na velike i male. Koncentracija TGF-β
je ispitivana pomoću ELISA testa, a dobijene vrednosti su analizirane u odnosu na grupe. Rezultati su pokazali povećanu produkciju TGF-β
u simptomatskim lezijama u odnosu na asimptomatske, međutim, razlika nije bila statistički značajna. Statistički značajna razlika u koncentraciji TGF-β
uočena je u grupi velikih lezija u poređenju sa malim (p<0,001). Čini se da TGF-β
ima modulirajući efekat na aktivnost resorpcije koštanog tkiva pod uticajem proinflamatornih citokina i može se smatrati molekularnim prognostičkim markerom zarastanja periapeksnih lezija.
Considering the limited knowledge regarding the effects of n-3 and n-6 PUFAs on the inflammatory response during physical activity, we aimed to evaluate the level of pro- and anti-inflammatory ...cytokines in young soccer players before and after a maximal physical load test at the beginning and end of a two-month training process. The study included 75 young footballers from Football School “Kragujevac,” who were followed during the two-month training programme. The subjects were divided into the following groups: 1) control group (consumed a standard diet); 2) group that consumed fish oil (2500 mg of n-3 PUFAs per day); 3) group that consumed nutritional sunflower oil (2500 mg of n-6 PUFAs daily). The maximal progressive exercise test was performed using a treadmill belt. Venous blood samples were drawn 4 times for the determination of cytokine levels (IL-6 and TNF-α): before and after the exercise load test before the two-month training programme (initial measurement) and immediately before and after the exercise load test after the two-month training programme (control measurement). Supplementation with fish oil (n-3) has been associated with reduced levels of IL-6 compared with the initial values. After an acute bout of exercise, n-3 PUFAs did not show a significant effect on inflammatory marker dynamics, whereas n-6 PUFAs slightly stimulated the production of TNF-α.
The aim of this study was to investigate the expression patterns of p16, p53 and VEGF in affected tissue and serum levels of cytokines TNF-α, IL-6, TGF-β and IL-17 in patients with ulcerative colitis ...(UC) and fistulating Crohn’s disease (CD). Serum levels of cytokines in patients with ulcerative colitis (n=24) and with Crohn’s disease (n=7) were analysed by ELISA. In colonoscopically obtained biopsies, p16, p53 and vascular endothelial growth factor expression were evaluated by immunohistochemistry.
The results of this study clearly show the predominance of pro-inflammatory type 1 and 17 immune response in patients with CD compared to those with UC. We believe that altered p16 and p53 induce enhanced VEGF expression and implicates enhanced production of pro-inflammatory TNF-α and IL-6. TNF-α and IL-6 further facilitate development of type 1/17 immune response.
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