Accuracy Of White Blood Cell Count, C-reactive Protein, Interleukin-6 And Tumor Necrosis Factor Alpha For Diagnosing Late Neonatal Sepsis

Objective: To evaluate the diagnostic value for late neonatal sepsis of white blood cell count (WBC) and assays for C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), in isolation and in conjunction. Methods: This was a diagnostic test validation study. Chemiluminescence was used to assay CRP, IL-6 and TNF-α at the time of clinical suspicion and again after 24 and 48 hours, whereas the WBC was performed only once, at the time of suspicion. Patients were classified into three groups based on clinical progress and culture results: confirmed sepsis (CS), probable sepsis (PS), and not infected (NI). Statistical analysiswas performed using the Wilcoxon and chi-square tests and Friedman analysis of variance; cutoffs were defined by plotting receiver operator characteristic curves. Results: The total study sample comprised 82 children, 42 of whom were classed as CS, 16 as PS and 24 as NI. At all three test times, the medians for CRP and IL-6 were significantly more elevated in the CS and PS groups, while the medians for TNF-α were abnormal only in the CS group. The CRP test had elevated indices of diagnostic utility at all three test times, better accuracy than the WBC and similar accuracy to the first IL-6 and TNF-α assays. There was no statistical difference between the cytokines, nor between them and the WBC. Combining tests did not increase diagnostic power, with the exception of the combination of WBC with CRP2 and when the sequential CRP assays were combined. Conclusions: Both CRP and WBC were useful for the diagnosis of late neonatal sepsis and comparable with IL-6 and TNF-α. Accuracy increased when CRP and WBC were combined and when sequential CRP assay results were used.846536542Klein, J., Marcy, M.S., Bacterial sepsis and meningitis (2005) Infectious diseases of the fetus & newborn infant, pp. 835-890. , Remington JS, Klein JO, editors, 6th ed. Philadelphia: WB Saunders;Lemons, J.A., Bauer, C.R., Oh, W., Korones, S.B., Papile, L.A., Stoll, B.J., Very low birth weigth outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996 (2001) Pediatrics, 107, pp. E1Mussi-Pinhata, M.M., Rego, M.A., Particularidades imunológicas do pré-termo extremo: Um desafio para a prevenção da sepse hospitalar. (2005) J Pediatr (Rio J), 81, pp. S59-S68Calil, R., Marba, S.T., von Nowakonski, A., Tresoldi, A.T., Reduction in colonization and nosocomial infection by multiresistant bacteria in a neonatal unit after institution of educational measures and restriction in the use of cephalosporins (2001) Am J Infect Control, 29, pp. 133-138Baltimore, R.S., Neonatal sepsis: Epidemiology and management (2003) Paediatr Drugs, 5, pp. 723-740da Silva, O., Ohlsson, A., Kenyon, C., Accuracy of leukocyte indices and C-reactive protein for diagnosis of neonatal sepsis: A critical review (1995) Pediatr Infect Dis J, 14, pp. 362-366Jackson, G.L., Engle, W.D., Sendelbach, D.M., Vedro, D.A., Josey, S., Vinson, J., Are complete blood cell counts useful in the evaluation of asymptomatic neonates exposed to suspected chorioamnionitis? (2004) Pediatrics, 113, pp. 1173-1180Ng, P.C., Diagnostic markers of infection in neonates (2004) Arch Dis Child Fetal Neonatal Ed, 89, pp. F229-FF35Gerdes, J.S., Diagnosis and management of bacterial infections in the neonate (2004) Pediatr Clin North Am, 51, pp. 939-959Kaufman, D., Fairchild, K.D., Clinical microbiology of bacterial and fungal sepsis in very low-birth-weight infants (2004) Clin Microbiol Rev, 17, pp. 638-680Stover, B.H., Shulman, S.T., Bratcher, D.F., Brady, M.T., Levine, G.L., Jarvis, W.R., Pediatric Prevention Network. Nosocomial infection rates in US children' s hospitals' neonatal and pediatric intensive care units (2001) Am J Infect Control, 29, pp. 152-157Stoll, B.J., Hansen, N., Infections in VLBW infants: Studies from the NICHD neonatal research network (2003) Semin Perinatol, 27, pp. 293-301Gaynes, R.P., Edwards, J.R., Jarvis, W.R., Culver, D.H., Tolson, J.S., Martone, W.J., Nosocomial infections among neonates in high-risk nurseries in the United States. National Nosocomial Infections Surveillance System (1996) Pediatrics, 98, pp. 357-361Manroe, B.L., Weinberg, A.G., Rosenfeld, C.R., Browne, R., The neonatal blood count in health and disease I. Reference values for neutrophilic cells (1979) J Pediatr, 95, pp. 89-98Silveira, R.C., Procianoy, R.S., Evaluation of interleukin-6, tumour necrosis factor-alpha and interleukin-1beta for early diagnosis of neonatal sepsis (1999) Acta Paediatr, 88, pp. 647-650Fanaroff, A.A., Korones, S.B., Wright, L.L., Verter, J., Poland, R.L., Bauer, C.R., Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network (1998) Pediatr Infect Dis J, 17, pp. 593-598Rodwell, R.L., Taylor, K.M., Tudehope, D.I., Gray, P.H., Hematologic scoring system in early diagnosis of sepsis in neutropenic newborns (1993) Pediatr Infect Dis J, 12, pp. 372-376Guillois, B., Donnou, M.D., Sizun, J., Bendaoud, B., Youinou, P., Comparative study of four tests of bacterial infection in the neonate. Total neutrophil count, CRP, fibrinogen and C3d (1994) Biol Neonate, 66, pp. 175-181Berger, C., Uehlinger, J., Ghelfi, D., Blau, N., Fanconi, S., Comparison of C-reactive protein and white blood cell count with differential in neonates at risk for septicemia (1995) Eur J Pediatr, 154, pp. 138-144Benitz, W.E., Han, M.Y., Madan, A., Ramachranda, P., Serial serum C-reactive levels in the diagnosis of neonatal infection (1998) Pediatrics, 102, pp. E41Ehl, S., Gering, B., Bartmann, P., Högel, J., Pohlandt, F., C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection (1997) Pediatrics, 99, pp. 216-221Chiesa, C., Pellegrini, G., Panero, A., Osborn, J.F., Signore, F., Assumma, M., Pacifico, L., C-reactive protein, interleukin-6, and procalcitonin in the immediate postnatal period: Influence of illness severity, risk status, antenatal and perinatal complications, and infection (2003) Clin Chem, 49, pp. 60-68Franz, A.R., Bauer, K., Schalk, A., Garland, S.M., Bowman, E.D., Rex, K., International IL-8 Study Group. Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: A multicenter, randomized, controlled trial (2004) Pediatrics, 114, pp. 1-8Procianoy, R.S., Silveira, R.C., A influência do tempo de coleta sobre os níveis de interleucina-6 na sepse neonatal precoce. (2004) J Pediatr (Rio J), 80, pp. 407-410Buck, C., Bundschu, J., Gallati, H., Bartmann, P., Pohlandt, F., Interleukin-6: A sensitive parameter for the early diagnosis of neonatal bacterial infection (1994) Pediatrics, 93, pp. 54-58de Bont, E.S., Martens, A., van Raan, J., Samson, G., Fetter, W.P., Okken, A., Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 plasma levels in neonatal sepsis (1993) Pediatr Res, 33, pp. 380-383Ng, P.C., Li, K., Wong, R.P., Chui, K., Wong, E., Li, G., Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections (2003) Arch Dis Child Fetal Neonatal Ed, 88, pp. F209-F213Panero, A., Pacifico, L., Rossi, N., Mancuso, G., Stegagno, M., Chiesa, C., Interleukin 6 in neonates with early and late onset infection (1997) Pediatr Infect Dis J, 16, pp. 370-375Roman, J., Fernandez, F., Velasco, F., Rojas, R., Roldan, M.R., Torres, A., Serum TNF levels in neonatal sepsis and septic shock (1993) Acta Paediatr, 82, pp. 352-354Ng, P.C., Cheng, S.H., Chui, K.M., Fok, T.F., Wong, M.Y., Wong, W., Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants (1997) Arch Dis Child Fetal Neonatal Ed, 77, pp. F221-F22

Serum Levels Of Interleukin-6 (il-6), Interleukin-18 (il-18) And C-reactive Protein (crp) In Patients With Type-2 Diabetes And Acute Coronary Syndrome Without St-segment Elevation [níveis Séricos De Interleucina-6 (il-6), Interleucina-18 (il-18) E Proteína C Reativa (pcr) Na Síndrome Coronariana Aguda Sem Supradesnivelamento Do St Em Pacientes Com Diabete Tipo 2]

Background: Atherosclerosis is an inflammatory disease, and serum levels of inflammatory markers such as interleukin 6 (IL-6), interleukin 18 (IL-18) and C-reactive protein (CRP) are used to evaluate patients with coronary artery disease. In patients with type-2 diabetes, atherosclerosis is related to a larger number of events such as myocardial infarction and death, when compared with patients without diabetes. Objective: To evaluate the inflammatory response in patients with diabetes and acute events of coronary instability. Methods: Two groups of patients were primarily selected. The first group was comprised of diabetic outpatients with stable angina (D-CCS) and presence of coronary artery disease on coronary angiography (n=36). The second group was comprised of diabetic patients seen in the emergency room with acute coronary syndrome (D-ACS) without ST-segment elevation (n=38). Non-diabetic patients with ACS (n=22) and CCS (n=16) comprised the control group. Serum levels of CRP, IL-6 and IL-18 were determined using nephelometry (CRP) and ELISA (IL-6 and IL-18) techniques. Results: Higher serum IL-6 levels were found in diabetic or non-diabetic patients with ACS than in the group with CCS. On the other hand, diabetic patients with ACS had higher CRP levels in comparison with the other groups. Serum IL-18 levels were not significantly different among the patients studied. Conclusion: our findings suggest a more intense inflammatory activity in patients with coronary instability. This inflammatory activity, as measured by CRP, seems to be even more intense in diabetic patients.9028690+94-99Libby, P., Molecular bases of the acute coronary syndromes (1995) Circulation, 91, pp. 2844-2850Aronson, D., Rayfield, E.J., Diabetes and obesity (1996) Atherosclerosis and Coronary Artery Disease, pp. 327-359. , Fuster V, Ross R, Topol EJ, eds, Philadelphia, Pa: Lippincott-Raven;Beckman, J.A., Creager, M.A., Libby, P., Diabetes and atherosclerosis: Epidemiology, pathophysiology, and management (2002) JAMA, 287, pp. 2570-2581ROSS, R., Atherosclerosis: An inflammatory disease (1999) N Engl J Med, 340, pp. 115-126Okamura, H., Tsutsui, H., Kashiwamura, S., Interleukin-18: A novel cytokine that augments both innate and acquired immunity (1998) Adv Immunol, 70, pp. 281-312Fantuzzi, G., Reed, D.A., Dinarello, C.A., IL-12-induced IFN-gamma is dependent on caspase-1 processing of the IL-18 precursor (1999) J Clin Invest, 104, pp. 761-767Sakkinen, P., Abbott, R.D., Curb, J.D., C-reactive protein and myocardial infarction (2002) J Clin Epidemiol, 55, pp. 445-451Katherine, E., Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans (2002) Circulation, 106, pp. 2067-2072Biasucci, L., Elevated Levels of Interleukin-6 in Unstable Angina (1996) Circulation, 94, pp. 874-877Ridker, P.M., C-Reactive Protein and Other markers of Inflammation in the Prediction of Cardiovascular Disease in Women (2000) N Engl J Med, 342, pp. 836-843Schönbeck U., Libby P . Inflammation, Immunity, and HMG-CoA Reductase Inhibitors: Statins as Antiinflammatory Agents? Circulation, Jun 2004109: II-18-II-26Yudkin, J.S., High levels of circulating proinflammatory cytokines and leptin in urban, but not rural, Indians. A potential explanation for increased risk of diabetes and coronary heart disease (1999) Diabetes Care, 22 (2), pp. 363-364. , Feb;Festa, A., Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study (2000) Kidney Int, 58 (4), pp. 1703-1710. , Oct;Kanemaki, T., Interleukin 1beta and interleukin 6, but not tumor necrosis factor alpha, inhibit insulin-stimulated glycogen synthesis in rat hepatocytes (1998) Hepatology, 27 (5), pp. 1296-1303. , May;Moreno, P.R., Coronary Composition and Macrophage Infiltration in Atherectomy Specimens From Patients With Diabetes Mellitus (2000) Circulation, 102, p. 2180Verma, S., Kuliszewski, M.A., Mickle, D.A.G., C-reative protein attenuates endothelial progenitor cell survival and differentiation (2002) Can J Cardiol, 18, p. 325Verma, S., Li, S., Badiwala, M.V., Weisel, R.D., Endothelin Antagonism and Interleukin-6 Inhibition Attenuate the Proatherogenic Effects of C-Reactive Protein (2003) Circulation, 105, pp. 1890-1896Santos, W.B., Mesquita, E.T., Vieira, R.M., Olej, B., Proteína-C- reativa e doença cardiovascular (2003) Arq Bras Cardiol, 80, pp. 452-456Duarte, E.R., Pellanda, L.E., Portal, V.L., Perfil Inflamatório, Metabólico e Lipídico na Síndrome Isquêmica Aguda: Relação com Eventos Intra e Pós-Hospitalares. (2005) Arq Brás Cardiol, 84, pp. 122-12

Placental Involvement In Paracoccidioidomycosis

A case of juvenile-type paracoccidioidomycosis in a pregnant woman is reported. The disease pre-dated pregnancy and antifungal treatment was being administered when she became pregnant. A premature male infant was delivered with no evidence of infection. Microscopic examination of the placenta showed numerous Paracoccidioides brasiliensis yeast forms in the intervillous space, enmeshed in a macrophagic-phagocytic reaction, with damage of the trophoblastic layer. Placental transfer of specific P. brasiliensis antibodies was demonstrated. © 1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.31324925

Immunocytochemical Localization Of Cytokines And Inducible Nitric Oxide Synthase (inos) In Oral Mucosa And Lymph Nodes Of Patients With Paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is a deep mycosis caused by Paracoccidioides brasiliensis, with high incidence in Brazil. In order to examine the immune response in lesional tissue from patients with PCM, we analyzed cytokines as well as the phenotype of the cell infiltrate. Paraffin-embedded tissue from the oral mucosa of eight patients with the localized adult form (AF) of PCM and from the lymph nodes of 10 patients with the juvenile form (JF) of PCM was analyzed by immunohistochemistry to detect tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10). Most of the inflammatory cells in the lymph nodes were CD68+ (macrophages, epithelioid and giant cells), while a mixed infiltrate with macrophages, plasma cells and neutrophils was detected in the oral mucosa. TNF-α as well as iNOS expression was similar in lymph nodes and oral mucosa, whereas TGF-β and IL-10 were observed in a larger number of macrophages, epithelioid and giant cells in the lymph nodes, where numerous yeast cells were visualized. The higher expression of anti-inflammatory cytokines (IL-10 and TGF-β) in lesions of patients with the JF of PCM (lymph nodes) may represent a mechanism by which the fungus evades the host immune response, contributing to a more severe and disseminated form of the disease. © 2003 Elsevier Science Ltd. All rights reserved.215234241Franco, M., Montenegro, M.R., Mendes, R.P., Marques, S.A., Dillon, N.L., Mota, N.G.S., Paracoccidioidomycosis: A recently proposed classification of its clinical forms (1987) Rev Soc Bras Med Trop, 20, pp. 129-132Del Negro, G., Lacaz, C.S., Zamith, V.A., Siqueira, A.M., General clinical aspects: Polar forms of paracoccidioidomycosis, the disease in childhood (1994) Paracoccidioidomycosis, pp. 225-232. , M. Franco, C.S. Lacaz, A. Restrepo-Moreno, & G. Del Negro. Boca Raton, FL: CRC PressFranco, M., Mendes, R.P., Moscardi-Bacchi, Rezkallah-Iwasso, M., Montenegro, M.R., Paracoccidioidomycosis (1989) Baillière's Clin Trop Med Commun Dis, 4, pp. 185-219Calich, V.L., Kashino, S.S., Cytokines produced by susceptible and resistant mice in the course of Paracoccidioides brasiliensis infection (1998) Braz J Med Biol Res, 31, pp. 615-623Souto, J.T., Figueiredo, F., Furlanetto, A., Pfeffer, K., Rossi, M.A., Silva, J.S., Interferon-gamma and tumor necrosis factor-alpha determine resistance to Paracoccidioides brasiliensis infection in mice (2000) Am J Pathol, 156, pp. 1811-1820Cano, L.E., Kashino, S.S., Arruda, C., Andre, D., Xidieh, C.F., Singer-Vermes, L.M., Protective role of gamma interferon in experimental pulmonary paracoccidiodomycosis (1998) Infect Immun, 66, pp. 800-806Mamoni, R.L., Nouér, S.A., Oliveira, S.J., Musatti, C.C., Rossi, C.L., Camargo, Z.P., Enhanced production of specific IgG4, IgE, IgA and TGF-β in sera from patients with the juvenile form of paracoccidioidomycosis (2002) Med Mycol, 40, pp. 153-159Oliveira, S.J., Mamoni, R.L., Musatti, C.C., Papaiordanou, P.M.O., Blotta, M.H.S.L., Cytokines and lymphocyte proliferation in juvenile and adult forms of paracoccidioidomycosis: Comparison with infected and non-infected controls (2002) Microbes Infect, 4, pp. 139-144Fornari, M.C., Bava, A.J., Guereño, M.T., Berardi, V.E., Silaf, M.R., Negroni, R., High serum interleukin-10 and tumor necrosis factor alpha levels in chronic paracoccidioidomycosis (2001) Clin Diag Lab Immunol, 8, pp. 1036-1038Silva, C.L., Silva, M.F., Faccioli, L.H., Pietro, R.C., Cortez, A.S., Foss, N.T., Differential correlation between interleukin pattern in disseminated and chronic human paracoccidioidomycosis (1995) Clin Exp Immunol, 101, pp. 314-320Kindler, V., Sappino, A.P., Grau, G.E., Piguet, P.F., Vassali, P., The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection (1989) Cell, 56, pp. 731-740Brummer, E., Hanson, L.H., Restrepo, A., Stevens, D.A., In vivo and in vitro activation of pulmonary macrophage by IFN-γ for enhanced killing of Paracoccidioides brasiliensis and Blastomyces dermatidis (1988) J Immunol, 140, pp. 2786-2789MacMicking, J., Xie, Q., Nathan, C., Nitric oxide and macrophage function (1997) Annu Rev Immunol, 15, pp. 323-350Green, S.J., Scheller, L.F., Marletta, M.A., Seguin, M.C., Klots, F.W., Slayter, M., Nitric oxide: Cytokine-regulation of nitric oxide in host resistance to intracellular pathogens (1994) Immunol Lett, 43, pp. 87-94Gazzinelli, R.T., Oswald, I.P., Hieny, S., James, S.L., Sher, A., The microbicidal activity of interferon-gamma-treated macrophages against Trypanosoma cruzi involves an L-arginine-dependent, nitrogen oxide-mediated mechanism inhibitable by interleukin 10 and transforming growth factor-beta (1992) Eur J Immunol, 22, pp. 2501-2506Gonzalez, A., Gregori, W., Velez, D., Restrepo, A., Cano, L.E., Nitric oxide participation in the fungicidal mechanism of gamma interferon-activated murine macrophages against Paracoccidioides brasiliensis conidia (2000) Infect Immun, 68, pp. 2546-2552Bocca, A.L., Silva, M.F., Silva, C.L., Cunha, F.Q., Figueiredo, F., Macrophage expression of class II major histocompatibility complex gene products in Paracoccidioides brasiliensis-infected mice (1999) Am J Trop Med Hyg, 61, pp. 280-287Nascimento, F.R.F., Calich, V.L.G., Rodriguez, D., Russo, M., Dual role for nitric oxide in paracoccidioidomycosis: Essential for resistance, but overproduction associated with susceptibility (2002) J Immunol, 168, pp. 593-4600Bocca, A.L., Hayashi, E.E., Pinheiro, A.G., Furlanetto, A.B., Campanelli, A.P., Cunha, F.Q., Treatment of Paracoccidioides brasiliensis-infected mice with a nitric oxide inhibitor prevents the failure of cell-mediated immune response (1998) J Immunol, 161, pp. 3056-3063Letterio, J.J., Roberts, A.B., Regulation of immune responses by TGF-β (1998) Annu Rev Immunol, 16, pp. 137-161Moore, K.W., Malefyt, R.W., Coffman, R.L., O'Garra, A., Interleukin-10 and the interleukin-10 receptor (2001) Annu Rev Immunol, 19, pp. 683-765Imhof, B.A., Dunon, D., Leukocyte migration and adhesion (1993) Adv Immunol, 58, pp. 345-41

Circulating Levels Of Chemokines In Psoriasis

Chemokines may contribute to local and systemic inflammation in patients with psoriasis. Previous studies have demonstrated the importance of chemokine ligands and receptors in the recruitment of T cells into psoriatic lesional skin and synovial fluid. The aim of this study was to evaluate the levels of Th1-related chemokines in psoriasis and to investigate any association with disease severity. We quantified serum levels of CXCL9, CXCL10 and CXCL16 and the frequencies of CD4+CXCR3+ T lymphocytes through ELISA and flow cytometry, respectively. A total of 38 patients with psoriasis and 33 controls were included. There were no significant differences in chemokine levels between psoriasis and control groups. Patients with psoriatic arthritis had lower median level of CXCL10 when compared with controls (p=0.03). There were no significant correlations between serum chemokines analyzed and disease severity. Frequencies of CD4+CXCR3+ T cells were lower in patients with psoriasis than in controls (p<0.01). A sensitivity analysis excluding patients on systemic therapy yielded similar results. Serum concentrations of CXCL9, CXCL10 and CXCL16 were not increased in the psoriasis group or correlated with disease severity. Systemic levels of chemokine ligands do not seem to be sensitive biomarkers of disease activity or accurate parameters to predict response to therapy. Frequencies of CD4+CXCR3+ T cells were decreased in the peripheral blood of psoriasis patients, possibly due to recruitment to inflammatory lesions.4815760Nestle, F.O., Kaplan, D.H., Barker, J., Psoriasis (2009) N. Engl. J. Med., 361, pp. 496-509Griffiths, C.E., Barker, J.N., Pathogenesis and clinical features of psoriasis (2007) Lancet., 370, pp. 263-271Cai, Y., Fleming, C., Yan, J., New insights of T cells in the pathogenesis of psoriasis (2012) Cell. Mol. Immunol., 9, pp. 302-309Byrne, F.R., Winters, A., Brankow, D., An antibody to IP-10 is a potent antagonist of cell migration in vitro and in vivo and does not affect disease in several animal models of inflammation (2009) Autoimmunity., 42, pp. 171-182Rottman, J.B., Smith, T.L., Ganley, K.G., Potential role of the chemokine receptors CXCR3, CCR4, and the integrin alphaEbeta7 in the pathogenesis of psoriasis vulgaris (2001) Lab. Invest., 81, pp. 335-347Chen, S.C., De Groot, M., Kinsley, D., Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions (2010) Arch. Dermatol. Res., 302, pp. 113-123Gunther, C., Carballido-Perrig, N., Kaesler, S., CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells (2012) J. Invest. Dermatol., 132, pp. 626-634Oh, S.T., Schramme, A., Tilgen, W., Overexpression of CXCL16 in lesional psoriatic skin (2009) Dermatoendocrinology., 1, pp. 114-118Antonelli, A., Fallahi, P., Delle Sedie, A., High values of alpha (CXCL10) and beta (CCL2) circulating chemokines in patients with psoriatic arthritis, in presence or absence of autoimmune thyroiditis (2008) Autoimmunity., 41, pp. 537-542Ekman, A.K., Sigurdardottir, G., Carlstrom, M., Systemically elevated Th1-, Th2-and Th17-associated chemokines in psoriasis vulgaris before and after ultraviolet B treatment (2013) Acta. Derm. Venereol., 93, pp. 527-531Horn, E.J., Fox, K.M., Patel, V., Are patients with psoriasis undertreated? Results of National Psoriasis Foundation survey (2007) J. Am. Acad. Dermatol., 57, pp. 957-962Yeung, H., Takeshita, J., Mehta, N.N., Psoriasis severity and the prevalence of major medical comorbidity: A population-based study (2013) JAMA Dermatol., 149, pp. 1173-1179Johnston, A., Arnadottir, S., Gudjonsson, J.E., Obesity in psoriasis: Leptin and resistin as mediators of cutaneous inflammation (2008) Br. J. Dermatol., 159, pp. 342-350Rosenblum, J.M., Shimoda, N., Schenk, A.D., CXC chemokine ligand (CXCL) 9 and CXCL10 are antagonistic costimulation molecules during the priming of alloreactive T cell effectors (2010) J. Immunol., 184, pp. 3450-3460Wuest, T., Farber, J., Luster, A., Carr, D.J., CD4+ T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection (2006) Cell. Immunol., 243, pp. 83-89Groom, J.R., Luster, A.D., CXCR3 ligands: Redundant, collaborative and antagonistic functions (2011) Immunol. Cell. Biol., 89, pp. 207-215Aeberli, D., Seitz, M., Juni, P., Villiger, P.M., Increase of peripheral CXCR3 positive T lymphocytes upon treatment of RA patients with TNF-alpha inhibitors (2005) Rheumatology (Oxford), 44, pp. 172-175Kunkel, E.J., Boisvert, J., Murphy, K., Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes (2002) Am. J. Pathol., 160, pp. 347-355Loos, T., Dekeyzer, L., Struyf, S., TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: Enhanced CXCL9 in autoimmune arthritis (2006) Lab. Invest., 86, pp. 902-916Call, D.R., Nemzek, J.A., Ebong, S.J., Ratio of local to systemic chemokine concentrations regulates neutrophil recruitment (2001) Am. J. Pathol., 158, pp. 715-721Flier, J., Boorsma, D.M., Van Beek, P.J., Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation (2001) J. Pathol., 194, pp. 398-405Goebeler, M., Toksoy, A., Spandau, U., The C-X-C chemokine Mig is highly expressed in the papillae of psoriatic lesions (1998) J. Pathol., 184, pp. 89-95Linkov, F., Gu, Y., Arslan, A.A., Reliability of tumor markers, chemokines, and metastasis-related molecules in serum (2009) Eur. Cytokine. Netw., 20, pp. 21-2

Enhanced Production Of Specific Igg4, Ige, Iga And Tgf-β In Sera From Patients With The Juvenile Form Of Paracoccidioidomycosis

Paracoccidioidomycosis (PCM) occurs in two distinct forms, the acute or juvenile form (JF), and the chronic or adult form (AF). To clarify the basis of this dichotomy, specific IgG subclasses, IgA and IgE anti-gp43 were measured by enzyme-linked immunosorbent assay, in patients with different forms of PCM. Serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, macrophage inflammatory protein (MIP)-1α and transforming growth factor (TGF)-β were also quantified. We show here that JF patients have significantly higher titers of IgE antibodies against gp43, an immunodominant antigen specific for Paracoccidioides brasiliensis, than do patients with the unifocal adult form (UF-AF, isolated lesions). Patients with the multifocal adult form (MF-AF, lesions in more than one organ) also produced elevated levels of anti-P. brasiliensis IgE. Furthermore, specific IgE levels were correlated with IgG4, IgA and eosinophilia. Patients with JF showed eosinophilia and increased levels of TGF-β, a switching factor for IgA. These results indicate a T helper (Th)-2 pattern of cytokine expression in both the JF and the MF-AF of PCM. On the other hand, patients with UF-AF had a significantly lower production of specific IgE, IgG4 and IgA than was seen in the other patient groups.402153159Blotta, M.H.S.L., Mamoni, R.L., Oliveira, S.J., Endemic regions of paracoccidioidomycosis in Brazil: A clinical and epidemiologic study of 584 cases in southeast region (1999) Am J Trop Med Hyg, 61, pp. 390-394Del Negro, G., Lacaz, C.S., Zamith, V.A., Siqueira, A.M., General clinical aspects: Polar forms of paracoccidioidomycosis, the disease in childhood (1994) Paracoccidioidomycosis, pp. 225-232. , In: Franco M, Lacaz CS, Restrepo-Moreno A, Del Negro G, eds.Boca Raton, FL: CRC PressFranco, M., Montenegro, M.R., Mendes, R.P., Paracoccidioidomycosis: A recently proposed classification of its clinical forms (1987) Rev Soc Bras Med Trop, 20, pp. 129-132Musatti, C.C., Reskallah, M.T., Mendes, E., Mendes, N.F., In vivo and in vitro evaluation of cell-mediated immunity in patients with paracoccidioidomycosis (1976) Cell Immunol, 24, pp. 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Pentoxifylline Reduces Pro-inflammatory And Increases Anti-inflammatory Activity In Patients With Coronary Artery Disease-a Randomized Placebo-controlled Study

The balance between different immunological stimuli is essential in the progression and stabilization of atherosclerotic plaques. Immune regulation has been suggested as potential target for the treatment of atherosclerotic disease. We sought to determine whether treatment with pentoxifylline, a phosphodiesterase inhibitor with immunomodulating properties, could reduce the pro-inflammatory response observed in patients with acute coronary syndromes (ACS) and increase anti-inflammatory activity. In a double-blind, prospective, placebo-controlled study, 64 patients with ACS were randomized to receive pentoxifylline 400 mg TID or placebo for 6 months. Analysis of the pro-inflammatory markers, C-reactive protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis factor (TNF)-α and the anti-inflammatory cytokines, transforming growth factor (TGF)-β1 and IL-10 were done at baseline, 1 and 6 months. Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-α compared to placebo after 6 months (P = 0.04 and P < 0.01, respectively). IL-12 increase was significantly less pronounced with pentoxifylline (P = 0.04). The levels of the anti-inflammatory cytokine, IL-10, also declined significantly less in the pentoxifylline group compared to placebo (P < 0.01) with a trend towards a higher increase of TGF-β1 in the former group (P = 0.16). Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory response in patients with ACS and may have beneficial clinical effects on cardiovascular events. © 2006 Elsevier Ireland Ltd. All rights reserved.1961434442Hansson, G.K., Inflammation, atherosclerosis, and coronary artery disease (2005) N Engl J Med, 352, pp. 1685-1695Frostegard, J., Ulfgren, A.K., Nyberg, P., Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines (1999) Atherosclerosis, 145, pp. 33-43Zhou, X., Paulsson, G., Stemme, S., Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice (1998) J Clin Invest, 101, pp. 1717-1725Uyemura, K., Demer, L.L., Castle, S.C., Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis (1996) J Clin Invest, 97, pp. 2130-2138Fernandes, J.L., Mamoni, R.L., Orford, J.L., Increased Th1 activity in patients with coronary artery disease (2004) Cytokine, 26, pp. 131-137Liuzzo, G., Vallejo, A.N., Kopecky, S.L., Molecular fingerprint of interferon-gamma signaling in unstable angina (2001) Circulation, 103, pp. 1509-1514Liuzzo, G., Biasucci, L.M., Gallimore, J.R., The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina (1994) N Engl J Med, 331, pp. 417-424Biasucci, L.M., Vitelli, A., Liuzzo, G., Elevated levels of interleukin-6 in unstable angina (1996) Circulation, 94, pp. 874-877Pinderski Oslund, L.J., Hedrick, C.C., Olvera, T., Interleukin-10 blocks atherosclerotic events in vitro and in vivo (1999) Arterioscler Thromb Vasc Biol, 19, pp. 2847-2853Grainger, D.J., Transforming growth factor beta and atherosclerosis: so far, so good for the protective cytokine hypothesis (2004) Arterioscler Thromb Vasc Biol, 24, pp. 399-404Cipollone, F., Fazia, M., Mincione, G., Increased expression of transforming growth factor-beta1 as a stabilizing factor in human atherosclerotic plaques (2004) Stroke, 35, pp. 2253-2257Mallat, Z., Tedgui, A., The role of transforming growth factor beta in atherosclerosis: novel insights and future perspectives (2002) Curr Opin Lipidol, 13, pp. 523-529Lutgens, E., Cleutjens, K.B., Heeneman, S., Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype (2000) Proc Natl Acad Sci USA, 97, pp. 7464-7469Zhao, L., Cuff, C.A., Moss, E., Selective interleukin-12 synthesis defect in 12/15-lipoxygenase-deficient macrophages associated with reduced atherosclerosis in a mouse model of familial hypercholesterolemia (2002) J Biol Chem, 277, pp. 35350-35356Laurat, E., Poirier, B., Tupin, E., In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice (2001) Circulation, 104, pp. 197-202Ramani, M., Khechai, F., Ollivier, V., Interleukin-10 and pentoxifylline inhibit C-reactive protein-induced tissue factor gene expression in peripheral human blood monocytes (1994) FEBS Lett, 356, pp. 86-88D'Hellencourt, C.L., Diaw, L., Cornillet, P., Differential regulation of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta, and IL-10 by pentoxifylline (1996) Int J Immunopharmacol, 18, pp. 739-748Ward, A., Clissold, S.P., Pentoxifylline. 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Detection Of Tcd4+ Subsets In Human Carotid Atheroma

Activated TCD4+ cells are detected in human atherosclerotic plaques which indicate their participation in disease progression and destabilization. Among these cells, IFN-γ-producing T cells (TH1) are recognized as having a pro-atherogenic role. Recently, the IL-17-producing T helper lineage of cells (TH17) has been identified in atherosclerotic lesions. They have been linked to atheroma development through the production of pro-inflammatory mediators present in these lesions. Furthermore, IL-22 producing TCD4+ cells (TH22) have been identified in the atheromatous environment, but their presence and function has not been investigated. The aim of this study was to analyze the immune response mediated by pro-inflammatory subtypes of TCD4+ cells in atheromatous lesions. Atherosclerotic plaques of 57 patients with critical stenosis of carotid submitted to endarterectomy were evaluated. Three carotid fragments from organ donors were used as control. mRNA analysis showed expression of TH1 (IFN-γ, T-bet, IL-2, IL-12p35, TNF-α and IL-18); TH2 (GATA-3); TH17 (IL-17A, IL-17RA, Rorγt, TGF-β, IL-6, IL-1β, IL-23p19, CCL20, CCR4 and CCR6) and TH22 (IL-22 and Ahr) related markers. Asymptomatic patients showed higher expression of mRNA of IL-10, TGF-β, CCR4 and GATA-3 when compared to symptomatic ones. Immunohistochemistry analysis showed higher levels of IL-23, TGF-β, IL-1β and IL-18 in macrophages and foam cells in unstable lesions compared to stable and control ones. In vitro stimulation of atheroma cells induced IL-17 and IFN-γ production. Finally we were able to detect, the following subpopulations of TCD3+ cells: TCD4+ IFN-γ+, TCD4+IL-17+, TCD4+IL-4+, TCD4+IL-22+ and double positive cells (IFN-γ/IL-17+, IFN-γ/IL-22+ or IL-17/IL-22+). 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