Irritable bowel syndrome in celiac disease - relationships to celiac disease antibodies and levels of pro-inflammatory cytokines / Síndrome del intestino irritable en la enfermedad celíaca: relaciones con los anticuerpos contra la enfermedad celíaca y los niveles de citocinas proinflamatorias

ABSTRACT Background: Evidence indicates that low-grade inflammation can alter gastrointestinal motor and sensory function and might contribute to the genesis of symptoms in IBS. Objective: To examine relationships between IBS, disease antibodies and cytokine titers in celiac patients and a control group. Materials and methods: IBS, CD activity and serum levels of IL-6, IL-8 and IL12/23p40 were determined in celiac patients and controls. Results: 123 celiac patients were included, 89% were female. 59% demonstrated disease activity and 32% met IBS criteria. Prevalence of IBS was not different between patients who adhered or did not adhere to GFD as well as between patients with or without positive antibodies. Celiac patients had increased levels of IL-6, IL-8 and IL12/23p40 as compared to controls. Higher levels of cytokines were found in celiac patients with IBS than in those without IBS. No difference in levels of cytokines was found between patients with and without CD positive antibodies. A significant negative correlation between the mental component of QoL and IL-6 and IL12/23p40 levels was found, but not with IL-8. Conclusion: Higher levels of inflammatory cytokines were found in CD patients with IBS than in either those without IBS or controls, indicating that IBS symptoms are associated with an increase in the inflammatory response and a decrease in quality of life of CD patients. These differences in cytokine levels were not related to CD antibodies status suggesting that IBS, in CD, is related to a different inflammatory process than that which is relevant to CD.

RESUMEN Antecedentes: la evidencia indica que la inflamación de bajo grado puede alterar la función motora y sensorial gastrointestinal y puede contribuir a la aparición de síntomas en el SII. Objetivo: Examinar la relación entre SII, anticuerpos contra enfermedades y títulos de citocinas en pacientes celíacos y un grupo de control. Materiales y métodos: se determinaron los síntomas de SII, actividad de CD y niveles séricos de IL-6, IL-8 e IL12 / 23p40 en pacientes celíacos y controles. Resultados: se incluyeron 123 pacientes celíacos, el 89% eran mujeres. El 59% demostró actividad de la enfermedad y el 32% cumplió con los criterios del SII. La prevalencia del SII no fue diferente entre los pacientes que se adhirieron o no se adhirieron a GFD, así como entre los pacientes con o sin anticuerpos positivos. Los pacientes celíacos tenían niveles aumentados de IL-6, IL-8 e IL12 / 23p40 en comparación con los controles. Se encontraron niveles más altos de citocinas en pacientes celíacos con SII que en aquellos sin SII. No se encontraron diferencias en los niveles de citocinas entre pacientes con y sin anticuerpos CD positivos. Se encontró una correlación negativa significativa entre el componente mental de la calidad de vida y los niveles de IL-6 e IL12 / 23p40, pero no con IL-8. Conclusión: Se encontraron niveles más altos de citocinas inflamatorias en pacientes con EC con SII que en aquellos sin SII o controles, lo que indica que los síntomas del SII están asociados con un aumento en la respuesta inflamatoria y una disminución en la calidad de vida de los pacientes con CD. Estas diferencias en los niveles de citocinas no estaban relacionadas con el estado de los anticuerpos contra la CD, lo que sugiere que el SII, en la CD, está relacionado con un proceso inflamatorio diferente al que es relevante para la CD.

Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria

BACKGROUND Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated. OBJECTIVE To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients. METHODS Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P. vivax malaria and 37 healthy donors from the same area (endemic control group - ENCG). FINDINGS Thrombocytopenia was the main manifestation in 55 patients, but was not associated with parasitaemia. The Pv-MAL patients showed increases in the mean platelet volume (MPV), which may be consistent with larger or megaplatelets. Contrary to the findings regarding the endemic control group, MPV and platelet distribution width (PDW) did not show an inverse correlation, due the increase in the heterogeneity of platelet width. In addition, the Pv-MAL patients presented increased IL-1β and reduced IL-12p70 and IL-2 serum concentrations. Furthermore, the reduction of these cytokines was associated with PDW values. MAIN CONCLUSIONS Our data demonstrate that an increase in MPV and the association between reductions of IL-2 and IL-12 and PDW values may be an immune response to thrombocytopenia in uncomplicated P. vivax malaria.

Níveis séricos de citocinas IL-2, IL-10 e IL-12 em pacientes com adenocarcinoma do estômago / Serum cytokine of il-2, il-10 and il-12 levels in patients with stomach adenocarcinoma

ABSTRACT BACKGROUND: Gastric adenocarcinoma is the fourth most common cause of cancer-associated death worldwide. OBJECTIVE: We evaluated the immunological status of patients with gastric cancer before surgery and circulating cytokines as potential diagnostic biomarkers for gastric cancer. METHODS: We included 90 healthy controls and 95 patients with distal Gastric adenocarcinoma in Mazandaran, Sari, Iran. We measured serum IL-2, IL-10 and IL-12 Levels by a sandwich enzyme-linked immunosorbent assay using the IBL international GMBH kit. RESULTS: The serum IL-10 levels in the patients with Gastric adenocarcinoma were significantly higher than those of the healthy controls (P=0.02). There were no significant differences in serum IL-2 and IL-12 levels between patients with gastric cancer and healthy controls. CONCLUSION: Increased levels of IL-10 might be useful as diagnostic biomarkers for Gastric adenocarcinoma; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. These results suggest that positive expression of IL-10 may be useful as a molecular marker to distinguish stage of gastric cancers which can be more readily controlled.

RESUMO CONTEXTO: O adenocarcinoma gástrico é a quarta causa mais comum de morte relacionada ao câncer em todo o mundo. OBJETIVO: Avaliar o status imunológico dos pacientes com câncer gástrico antes da cirurgia e as citocinas circulantes como potenciais biomarcadores diagnósticos para câncer gástrico. MÉTODOS: Incluímos 90 indivíduos controles saudáveis e 95 pacientes com adenocarcinoma gástrico distal em Mazandaran, Sari, Iran. Os níveis de soro Il-2, IL-10 e Il-12 foram medidos por um ensaio de imunoabsorção enzimática pela técnica de sanduíche usando o kit IBL International GmbH. RESULTADOS: Os níveis séricos IL-10 nos pacientes com adenocarcinoma gástrico foram significativamente superiores aos dos controles saudáveis (P=0,2). Não houve diferenças significativas nos níveis de soro IL-2 e IL-12 entre pacientes com câncer gástrico e controles saudáveis. CONCLUSÃO: Níveis aumentados de IL-10 podem ser úteis como biomarcadores diagnósticos para adenocarcinoma gástrico; no entanto, isso precisa ser confirmado com maior número de pacientes e com grupos de controle que não sejam doadores de sangue, adequadamente emparelhado por idade. Estes resultados sugerem que a expressão positiva do IL-10 pode ser útil como um marcador molecular para distinguir a fase de câncer gástrico que pode ser mais facilmente controlada.

Interleukin-12 as a biomarker of the beneficial effects of food restriction in mice receiving high fat diet or high carbohydrate diet

The impact of food restriction (FR) during 56 days on serum levels of cytokines in mice fed a high-fat diet (HFD) or high-carbohydrate diet (HCD) were evaluated. The amount of food was reduced 50% for HFD-FR and HCD-FR groups compared to mice receiving free access to HFD (HFD group) or HCD (HCD group). We quantified the serum levels of basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor, inducible protein 10, interferon γ, interleukin 1α (IL-1α), IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, keratinocyte chemoattractant, macrophage inflammatory protein-1α, monocyte chemotactic protein 1, monokine induced by IFN-γ, and tumor necrosis factor α. Only IL-12 levels were lower (P<0.05), for both HFD-FR (HFD-FR vs HFD) and HCD-FR (HCD-FR vs HCD). Therefore, IL-12 levels could be considered a biological marker of the beneficial effects of FR.

Paradoxical response to antituberculous therapy

A paradoxical response in a patient infected with tuberculosis is generally defined as the clinical or radiological worsening of pre-existing tuberculous lesions or the development of new lesions in a patient who initially improves with anti-tuberculosis therapy. It occurs in about 5% of patients with a clinical diagnosis of Mycobacterium tuberculosis infection. Since a rapid and accurate diagnostic test is lacking, the diagnosis of this paradoxical phenomenon can only be ascertained when other differential diagnoses such as secondary infections, inadequate anti-tuberculosis therapy as a result of drug resistance, poor compliance, and adverse reactions due to therapy are excluded

Prominent IL-12 Production and Tumor Reduction in Athymic Nude Mice after Toxoplasma gondii Lysate Antigen Treatment

Toxoplasma gondii is an intracellular protozoan parasite that causes a Th1 cellular immunity. Our previous study showed that T. gondii lysate antigen (TLA) treatment in S180 tumor-bearing mice resulted in tumor reduction by suppressing CD31 expression, a marker of angiogenesis. In the present study, to investigate tumor suppressive effect of TLA under the absence of T lymphocytes, athymic nude mice were compared with euthymic mice in the anti-tumorigenic effect triggered by TLA in CT26 tumors. According to the results, intratumorally injected TLA reduced tumor growth and TIMP-1 level, a metastatic marker, in both euthymic and athymic mice. TLA treatment led to a sharp increase in IL-12 expression in serum cytokine profiling of athymic mice, and increased MyD88 signals in macrophages derived from the bone marrow, implying the activation of innate immunity. The selective induction of IL-12 by TLA treatment had an anti-tumorigenic effect.

Interleukins 12 and 13 levels among beta-thalassaemia major patients

The role of inflammatory cytokines in the pathophysiology of beta-thalassaemia is still unclear. In this study production levels of interleukins [IL]-12 and IL-13 were measured by commercial ELISA in cultureI supernatants of mitogen-stimulated peripheral blood mononuclear cells from 30 non-splenectomized beta-thalassaemia cases with iron overload and 20 age- and sex-matched healthy individuals. IL-12 levels were significantly lower among cases compared with controls [91.4 pg/mL versus 154.6 pg/mL] while IL-13 levels were significantly higher [42.5 pg/mLversus 5.7 pg/mL]. There was a significant negative correlation between IL-12 and IL-13 levels among beta-thalassaemia cases [r= -0.42]. Patients with beta-thalassaemia alone had higher IL-12 levels than beta-thalassaemia patients who were seropositive for chronic hepatitis B or C virus Infection [140 pg/mL versus 50 pg/mL]; IL-13 levels were slightly lower [65 pg/mL versus 67 pg/mL]. An imbalance In the IL-12/IL-13 axis may be relevant to the pathophysiology of beta-thalassaemia

Interleukin-12 and interferon gamma levels in infants with post BCG lymphadenitis

Bacille Calmette Guerin [BCG] is a live bacterial vaccine used in many countries to prevent tuberculosis [TB]. However, because the vaccine consists of live attenuated bacteria, there is still a risk that inoculation with this Mycobacterium bovis strain in immunodeficent infant will cause localized [BCGitis] or disseminated infection, referred to as 'BCG-osis'[1,2] This was prospective hospital based study aiming to determine the serum levels of interleukin-12 and interferon-y among infants with post BCG lymphadenitis. The study included 20 cases [mean +/- SD of age was 4.2 +/- 1.7 months] with newly diagnosed post BCG lymphadenitis group in addition to 20 apparently healthy infants age and sex matched [mean +/- SD of age was 3.9 +/- 1.9 months] as a control group. The study was conducted during the period from March 2008 to November 2010. Both patients and controls were recruited from Paediatric Outpatients Clinics and Paediatric Emergency Department in Assiut University Children Hospital, Egypt. Written informed consents were obtained from the parents of both patients and controls. All cases were subjected to a thorough history, full clinical examinations and investigations which include routine blood tests, immunological studies and serum levels of Interleukin -12 and interferon- gamma. In the post BCG lymphadenitis group, 85% of cases came from rural areas, 45% have positive consanguinity, while 20% of the same group have positive family history of post BCG lymphadenitis. Serum IL-12 and IFN-gamma levels were significantly deceased in cases of post BCG lymphadenitis compared with control group [P< 0.01]. Serum IL-12 and IFN-gamma levels were significantly and positively correlated with age in studied cases. In addition, IL-12 was positively and significantly correlated with IFN-gamma. Serum IL-12 and IFN-gamma levels should be assessed in infants with post BCG lymphadenitis to detect IL-12/ IFN-gamma axis abnormalities. BCG vaccination should be delayed in every newborn and infant with a family history of post BCG lymphadenitis until immunodeficiency diseases and IL-12/IFN-gamma axis abnormalities have been ruled out

Interleukin [IL]-12, IL-5 and total IgE in hepatosplenic schistosomiasis with or without asthma

There are a number of similarities between protective immune responses against schistosomiasis and asthma. Both are associated with elevated concentrations of IgE and eosinophilia. Chronic schistosomiasis is liked to Th1 like response with involvement of pro-inflammatory cytokines in schistosomal hepatosplenic disease process resulting in low level of IL-S. Meanwhile, association with asthma could modulate the immune response with shift to Th2 side resulting in marked elevation of IL-5 and eosinophilia. This work evaluated the levels of serum IgE, IL-5 and IL-12 in Schistosoma mansoni-infected asthmatic patients. A total of 100 subjects selected from Al-Azhar University's Hospitals were divided into three groups GI: 50 patients with hepatosplenic schistosomiasis associated with asthma. GII: 25 patients with hepatosplenic schistosomiasis without apparent asthma. GIII: 25 patients with neither bilharzial liver cirrhosis nor asthma as control group. All patients were subjected to full history taking and clinical examination, pulmonary function tests, total serum IgE, bilharzial antibody titre, stool and urine examination for parasites, liver function tests and serum IL-5 and IL-12. The results showed very high level of the total serum IgE in GI and GII compared to GIII. There was high significant difference in peripheral blood eosinophil%. GI and GII gave highest levels, IL-5 was elevated in GI, but low GII, IL-12 was high in GII than GI

[Evaluation the relationship between alleles of+1188 in region of IL-12 with serum level of cytokine in patients with occult HBV infection]

Occult hepatitis B infection [OBI] is a form of hepatitis, which in despite of absence of detectable HBsAg, HBV-DNA is present in peripheral blood of patients. Evaluation the relationship between alleles of+1188 in region of IL-12 with serum level of cytokine in patients with occult HBV infection. In this study, the plasma samples of 3700 blood donors were tested for HBsAg and anti-HBc by ELISA. The HBsAg negative ve and anti-HBc positive samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples assigned as OBI cases and PCR-SSP and ELISA were performed to examine the polymorphisms in region of [+1188 and serum level of IL-12] respectively. The results showed that there is a significant difference in CC allele of+1188 region of IL-12 in two groups and no difference in the other evaluated genes. There is not any significant difference in serum level of IL-12 between OBI patients and controls. Our results also showed that there isn't any significant statistically relation between alleles of+ 1188 region of IL-12 with serum level of cytokine. According to the results of this study it could be concluded that OBI patients unable to produce enough quantity of IL-12 and it may be related to different IL-12 gene. CC allele was associated with OBI, hence, it seems that +1188 region of IL-12 gene has an important role in expression of IL-12 gene. Evaluation of relation between polymorphisms in +1188 region of IL-12 gene and its expression. In vitro and under mitogene affect can useful because no association was seen between serum level of IL-12 and alleles of this region

role of Thrombomodulin, IL-12, transforming growth factor-beta2 in early onset preeclamsia: a potential biomarker for disease severity

Early onset Preeclampsia is a pregnancy specific heterogeneous syndrome with genetic predisposition ranging from hypertension, proteinuria and edema to severe preeclampsia with complications. A defective implantation and placentation, circulating factors including proinflammatory molecules, cytokines and adhesion molecules have been implicated in the pathogenesis of preeclampsia. Was to assess the clinical value of assaying maternal serum concentration of thrombomodulin [TM] interleukin-12 [IL-12] and transforming growth factor beta-2 [TGF-beta 2], in normotensive, mild and severe preeclamptic pregnant women, and to evaluate the correlation between these factors and the blood pressure, uric acid and creatinine. The second objective was to look for differences between mild and severe early onset preeclampsia, compared with a healthy pregnant and non pregnant cross sectional investigated groups. Serum TM, IL-12 and TGF-beta 2 were measured using enzyme linked immunoassay [ELISA] and enzyme immunoassay respectively in 45 women with preeclampsia divided into 24 mild and 21 severe preeclamptic patients and compared with 21 pregnant normotensive and 20 non pregnant controls. Serum uric acid and creatinine were measured as well. Severe preeclamptic women had significantly increased levels of TM [p<0.01], IL-12 [p<0.01] and TGF-beta 2 p<0.01] compared with women with normal pregnancy and non pregnant women. Serum creatinine and uric acid co1Icentrations were significantly higher in severe preeclamptic patients [1.35 +/- 0.17mg/dL, 7.43 +/- 0.74mg/dL, respectively, mean +/- SD] and did not change significantly in mild preeclamptic women compared with those of healthy normotensive pregnant women. Significant positive correlations existed between serum TGF-beta 2 concentrations and mean arterial blood pressure, TM. serum creatinine and uric acid concentrations in severe pre peclamptic patients. Conclusion: Increase concentration of thrombomodulin, II-12 and TGF-beta 2, in severe preeclamptic patient might explain the shallow placentation, endothelial cell dysfunction and renal involvement described in severe preeclampsia. Measurement of maternal plasma of TM, IL-l2, TGF-beta 2 levels in preeclampsia can be useful biomarker for the assessment of the severity of the disease

Effect of SLE on IL-12 level as compared with other autoimmune rheumatic diseases

IL-12 is a proinflammatory cytokine produced by different antigen presenting cells. It has been shown to exert a critical role in inducing Th1 phenotype, thus initiating cell-mediated immune responses, but the significance of IL- 12 in rheumatic diseases is not clear. To determine IL-12 serum levels in autoimmune rheumatic diseases and to analyze the relationship of this cytokine with main clinical and laboratory parameters. We analyzed, by ELISA, serum IL-12 levels in 109 patients with Systemic Lupus Erythematosus [SLE], 42 with Sjogren Syndrome [SS], 27 with Systemic Sclerosis [Scl], 79 with Rheumatoid Arthritis [RA], 40 with Psoriatic Arthritis [PA] and 20 healthy controls. We also examined main clinical and laboratory parameters, including autoantibody profile and clinical indices of disease activity. IL-12 serum levels were significantly higher in SLE and SS patients in respect to controls. IL-12 serum levels were significantly higher in SLE patients as compared to those suffering from RA, PsA and Scl. When we evaluated disease activity in SLE patients, we found significantly higher IL-12 serum levels in subjects without renal involvement, while no correlation was found in the other rheumatic autoimmune diseases. These findings suggest that IL-12, modulating cell and humoral immune responses, are involved in the pathogenesis of autoimmune rheumatic diseases, such as SLE and SS

Serum levels of TNF-alpha, TNF-alpha RI, TNF-alpha RII and IL-12 in treated Rheumatoid Arthritis patients

Rheumatoid arthritis [RA] is a chronic multisystem autoimmune disease common in all races and ethnics. Cytokines and cytokines receptors play an important role in RA pathogenesis and clinical presentation. To investigate the serum levels of TNF-alpha, TNF-alpha RI, TNF-alpha RII and IL-12 in RA patients and healthy control group. In this study 43 patients fulfilling the revised criteria of American College of Rheumatology [ACR] for RA and 13 healthy cases as a control group were selected for TNF-alpha, TNF-alpha RI, TNF-alpha RII and IL-12 serum level analysis. The patients' age was 42.2 +/- 22 and the age of healthy group was 40.1 +/- 19.2 years [p=0.1]. The patients had an active disease with at least six swollen and ten tender joints. Minimum ESR was 28 mm at first hours of the morning. Early morning stiffness in patients lasted longer than 45 minutes. Our study showed that IL-12 serum level of the patients [91.69 +/- 43.07 [rho]g/ml] and control [61.79 +/- 40.08 [rho]g/ml] group was significantly different [p<0.001]. The serum level of TNF-alpha RI was 2.36 +/- 0.77 ng/ml in the patient and 1.73 +/- 0.37 ng/ml in the control group [p<0.01]. TNF-alpha RII serum concentration in patients was 8.89 +/- 2.3 ng/ml, while that of control group was 7.06 +/- 1.30 ng/ml [p=0.03]. The serum level of TNF-alpha in patients was 32.90 +/- 19.27 [rho]g/ml and that of the control group was 24.27 +/- 8.28 [rho]g/ml [p=0.08] with no significant difference between the two. It is concluded that IL-12, TNF-alpha RI and TNF-alpha RII serum concentrations are more important and better predictive factors than TNF-alpha in RA course and in the active forms of the disease

Prognostic improvement of patients with advanced liver cancer after active hexose correlated compound (AHCC) treatment.

Most patients with liver cancer are diagnosed when they are not suitable for resection. Although some palliative approaches can be applied to these patients, the overall survival rate remains unsatisfactory. Active hexose correlated compound (AHCC), a newly developed functional food, has been shown to act as a potent biological response modifier in in vitro experiments. Recently, AHCC was found to improve the prognosis of hepatocellular carcinoma patients following surgical treatment. We investigated whether AHCC could prolong survival and improve the prognosis of patients with advanced liver cancer. A prospective cohort study was performed with 44 patients with histologically confirmed liver cancer. All of the patients underwent supportive care. Survival time, quality of life, clinical and immunological parameters related to liver function, cellular immunity, and patient status were determined. Of the 44 patients, 34 and 10 received AHCC and placebo (control) orally, respectively. Patients in the AHCC treated-group had a significantly prolonged survival when compared to the control group by Mann-Whitney test (95% CI, p = 0.000). Quality of life in terms of mental stability, general physical health status, and ability to have normal activities were significantly improved after 3 months of AHCC treatment when tested using the Wilcoxon signed-rank test (on one-sided test, p = 0.028, 0.037, and 0.040, respectively). The apparent different clinical parameters between the two groups were the levels of albumin and percentage of lymphocytes with p-values of 0.000 and 0.026 at 1 and 2 months after treatment, respectively. Unlike the control patients, AHCC treated-patients with longer survival time had the tendency of better outcomes since the levels of AST and ALT had not increased rapidly from their baselines at follow-up. In addition, the levels of total IL-12 and neopterin were slightly increased in AHCC treated-patients. This study suggests that AHCC intake could prolong the survival and improve the prognosis of patients with advanced liver cancer and delay the gradual decline of their physiological status.

Proinflammatory cytokines [IL-12 and IL-18] in immune rheumatic diseases: relation with disease activity and autoantibodies production

lnterleukin-18 [IL-18] and its inducer IL-12 have multiple biological activities that are important in generating Th1 responses and inflammatory tissue damage. We investigated serum concentration of the novel pro-inflammatory Th1 cytokine; IL-18, and its inducer IL-12 in patients with immune rheumatic diseases. Group I comprised 32 patients of systemic lupus erythmatosus [SLE], Group II comprised 36 patients of rheumatoid arthritis [RA]. Group III comprised 9 patients [2 patients of Behcet, 2 patients of Dermatomyositis, 2 patients of Sicca syndrome, one patient of Scleroderma, and 2 patients of Mixed connective tissue disease]. Group IV is a control group consists of 21 sex and age matched healthy subjects and correlated their levels with autoantibody concentration [ANA and ds-DNA], clinical grades and SLE disease activity index [SLEDAI]. Serum IL-18, IL-12 ,ANA and ds-DNA were measured by enzyme immune sorbent assay. IL-18, IL-12 and ANA were significantly higher in the three studied groups than in the control group [IL-18; P<0.001 in the three groups, IL-12; P=0.019, P=0.002, and P= 0.006, and ANA; PO.001, P=0.002,and P=0.006, respectively].ds-DNA was significantly higher in SLE patients than in control group [P<0.001].There were significant positive correlations between; A] levels of IL-18,and both ANA and ds-DNA in SLE patient [r=0.41,P=0.001, r= 0.58 and P=0.001 respectively]; and B] IL-18 and ANA in both RA and group III patients [r= 0.32, P=0.005,r=0.61 and P= 0.022 respectively]. Also, there were significant positive correlation between the levels of IL-18 and clinical grades of the three groups [r=0.60, P=0.001, r=0.79, P=0.001, r=0.78 and P= 0.001 respectively]. In SLE patients ,IL-18 concentration shows significant positive correlation with SLEDAI score [r= 0.76 ,P=0.001]. In conclusion, the elevation of proinflammatory cytokines [IL-18 and IL-12] may trigger the inflammatory process in immune rheumatic diseases and IL-18 is correlated with disease activity

Immunological studies on mice vaccinated with irradiated cercaria and IL-12 against schistosoma mansoni infection

Protective immunity against Schistosoma mansoni infection correlates with increased levels of IgE and blood eosinophilia which are considered as markers of anti-parasitic cell-mediated immunity. IL-5 participates as well in the induction and regulation of IgE and eosinophilia, consequently in the development of acquired immunity. Swiss Webster female mice were subcutaneously injected with either 50 micro g of gamma-irradiated cercarial homogenate [400 Gy] twice weekly for three weeks alone or plus a single dose of IL-12 [0.8 ng/Kg]. The efficiency of immunization regimens were assessed 45 days post infection with 100 live cercariae/mouse by the number of worm burden, ova count, production of IL-5, eosinophils, and IgE levels in the vaccinated groups compared with the non-immunized group. The results demonstrated a significant reduction of ova count in the livers of vaccinated groups [57.19 and 40.13%] and worm couples compared with the non -immunized group. Furthermore, a decrease of IL-5 level as well as eosinopenia was recorded in both vaccinated groups. Scanning electron microscope [SEM] of adult worms recovered from the immunized groups revealed marked damage on the tegumental surface in males rather than females as well as constrictions and intensive corrugation of intertubercles

Contribution of interleukin 12 [IL-12] to immunologic responses in bronchial asthma and other lung diseases

Interleukin 12 [IL-12] is an important cytokine produced by monocytes and macrophages. It up regulates Th1 cytokines production especially IFNgamma and inhibits the expression of Th2 cytokines, so, its main function is the regulation of the bias of the immune system towards Th1 or Th2 response through a balance with IL-4 early in the immune response. This work was done to evaluate the serum and bronchoalveolar lavage [BAL] IL-12 in asthmatic patients compared with tuberculous patients and patients with primary lung cancer, to assess the impact of IL-12 on Th1-Th2 cytokines profile which determine the type of the response in these different diseases and to propose its potential clinical usefulness. The study included 4 groups: group I consisted of 20 asthmatic patients, group II: 10 patients who had pulmonary TB, group III: 10 patients with bronchogenic carcinoma, and group IV: 20 normal individuals. For all groups IL-12 was estimated in serum and [BAL] fluid using ELISA technique. Considering the results, IL-12 was significantly decreased in asthmatic patients and it increased with hyposensitiz ation, highly significantly increased in active pulmonary TB and significantly increased in localized bronchogenic carcinoma. It was concluded that IL-12 plays a central role on Th1-Th2 cytokines balance, being decreased in allergic conditions, i.e., producing immunological Th2, shift which is corrected to Th1 pathway by hyposensitization, hence, it may be of diagnostic and therapeutic values in bronchial asthma

Synergistic immunosuppression by candida in HIV infection: a cytokine based analysis.

Candida is a common opportunistic pathogen in HIV infection and is regarded a signal infection for progression to AIDS. Cytokine imbalances between Th1/Th2 groups have been described in both candida and HIV infections. A study was undertaken to assess the role of candida in furthering immunosuppression in HIV infection based on cytokine levels and CD4 cell counts. 30 Indian subjects were enrolled; 10 HIV positive patients with and 10 without mucosal candidiasis and 10 age matched controls. Th1 cytokines; interleukin (IL) 2, IL 12 and interferon (IFN) gamma, Th2 cytokines; IL 4, IL 6, IL 10 and tumor necrosis factor (TNF) alpha with CD 4 cell counts were estimated using ELISA in all subjects. CD4 cell counts were reduced in both patient groups as compared to controls; significantly more in patients with both HIV and candida infections. There was a decrease in Th1 cytokine levels in all patients; lower levels of Th1 cytokines were seen in patients with both infections. Among the Th2 cytokines, there was a significant increase in the levels of IL 6, IL 10 and TNF alpha in both patient groups; IL 10 and TNF alpha values were significantly raised in patients with dual HIV and candida infections as compared to the other patients. There was no difference in IL 4 values across the subject groups. A positive correlation between CD4 cell counts and Th1 cytokine levels and a negative correlation with Th2 cytokines were noted; these were stronger in patients with both HIV and candidiasis. Thus, there was a Th1/Th2 cytokine imbalance with CD4 cell count reduction in all HIV infected patients, which was more pronounced in patients with both infections. It can be concluded that, owing to the depressed CD4 cell count and Th1 response and increased Th2 cytokines in patients with both candidiasis and HIV as compared to patients with only HIV candidiasis may have a synergistic immunosuppressive effect with HIV in patients with dual infections.

Complicated malaria is associated with differential elevations in serum levels of interleukins 10, 12, and 15.

Complicated malaria, caused by Plasmodium falciparum, is characterized by multiple organ dysfunction. The pathogenesis of complicated malaria involves complex host-parasite interactions that include polarized cytokine responses. Recently, correlates between Th1-like and Th2-like cytokines, especially interleukin-10 (IL), IL-12, and TNF-alpha, and specific types of organ dysfunction have been noted. Here, we measured IL-10, IL-12, and for the first time, IL-15, in 19 patients aged 16-55 years old with complicated malaria on days 0 (admission), 3, 7, and 14. For analysis, patients were grouped together or sub-categorized into hyperparasitemias or cerebral malaria (CM). For IL-10, a dramatic increase was noted on admission, followed by a reduction toward control values that closely paralleled parasite clearance. For IL-12, modest but persistent increases were noted over the entire 14 day period that did not correlate with parasitemia. In general, especially on days 0 and 3, hyperparasitemic patients had, in comparison with CM patients, higher IL-10 and IL-12 levels. In contrast, IL-15 was generally below detection in most samples. These results provide further insight into the pathogenesis of complicated malaria by strengthening the contention that cytokines such as IL-10 and IL-12 are involved in modulating the immune response to P. falciparum.

Respuesta TH1 en la infeccion experimental con Trypanosoma cruzi / TH1 response in the experimental infection with Trypanosoma cruzi

En el huésped infectado con Trypanosoma cruzi, la respuesta inmune protectora involucra principalmente la producción de anticuerpos específicos y la activación de células fagocíticas por interferon-gamma (IFN-gamma). El efecto central del IFN-gamma in vivo sería la activación de la sintetasa inducible de óxido nítrico de macrófagos (iNOS) y la generación de óxido nítrico (NO§) que participa en la destrucción intracelular de los parásitos. En la infección aguda, la inducción de la respuesta TH1 sería llevada a cabo por la interleuquemia 12 (IL-12), que estimula la producción de IFN-gamma en células NK. En la liberación de IFN-gamma también intervienen otros tipos de células, como los linfocitos Thy-1 +CD4-CD4-CD8-, CD4+ y CD8+. El control de la respuesta TH1, podría ser, en parte, el resultado de la menor activación de macrófagos, por la disminución de la carga parasitaria, y de la producción de IL-10 y del factor de trasnformación del crecimiento beta (TGF-beta). La respuesta protectora TH1 también estaría implicada en el daño tisular y en las alteraciones de la respuesta inmune observadas durante la infección. Nosotros estudiamos la cinética de la actividad NK y de la producción de IL-12 e IFN-gamma por células de bazo, así como los niveles séricos de estas citoquinas centrales de la respuesta TH1, en ratones BALB/c y C3H infectados con T. cruzi, cepa Tulahuén. Inmediatamente después de la infección encontramos que, en las células de bazo, incrementó tanto la producción de IL-12 como la actividad NK, y este efecto fue mayor en ratones C3H que en BALB/c. En los C3H, el IFN-gamma aumentó simultáneamente, a diferencia de los BALB/c en los que la citoquina incrementó más tardíamente en la fase aguda. Em ambas cepas, la infección indujo muy rápidamente altos niveles séricos de IL-12 que se mantuvieron elevados durante toda la fase aguda. Por otro lado, el IFN-gamma sérico incrementó unos días antes del pico de parasitemia y alcanzó mayor concentración, y más tempranamente, en los ratones BALB/c que en los C3H. Para nuestra sorpresa, en la fase crónica de la infección, la producción de IL-12 seguía alta en ambas cepas, a pesar de ello, el IFN-gamma sólo continuó elevado en los ratones BALB/c. Aunque en la fase aguda la respuesta global fue predominantemente TH1 en las dos cepas de ratones, los BALB/c tienen una mayor susceptibilidad que los C3H...