Assessing endocrine and immune parameters in human immunodeficiency virus-infected patients before and after the immune reconstitution inflammatory syndrome

ABSTRACT Objective The present study compares immune and endocrine parameters between HIV-infected patients who underwent the Immune Reconstitution Inflammatory Syndrome (IRIS-P) during antiretroviral therapy (ART) and HIV-patients who did not undergo the syndrome (non-IRIS-P). Materials and methods Blood samples were obtained from 31 HIV-infected patients (15 IRIS-P and 16 non-IRIS-P) before ART (BT) and 48 ± 2 weeks after treatment initiation (AT). Plasma Interleukin-6 (IL-6) and Interleukin-18 (IL-18) were determined by ELISA. Cortisol, dehydroepiandrosterone sulfate (DHEA-S) and thyroxin concentrations were measured using chemiluminescence immune methods. Results Concentrations of IL-6 (7.9 ± 1.9 pg/mL) and IL-18 (951.5 ± 233.0 pg/mL) were significantly higher (p < 0.05) in IRIS-P than in non-IRIS-P (3.9 ± 1.0 pg/mL and 461.0 ± 84.4 pg/mL, respectively) BT. Mean T4 plasma level significantly decreased in both groups of patients after treatment (p < 0.05). In both groups cortisol levels were similar before and after ART (p > 0.05). Levels of DHEA-S in IRIS-P decreased AT (1080.5 ± 124.2 vs. 782.5 ± 123.8 ng/mL, p < 0.05) and they were significantly lower than in non-IRIS-P (782.5 ± 123.8 vs. 1203.7 ± 144.0 ng/mL, p < 0.05). IRIS-P showed higher values of IL-6 and IL-18 BT and lower levels of DHEA-S AT than in non-IRIS-P. Conclusion These parameters could contribute to differentiate IRIS-P from non-IRIS-P. The significant decrease in DHEA-S levels in IRIS-P after ART might suggest a different adrenal response in these patients, which may reflect the severity of the disease.

Extremely elevated IL-18 levels may help distinguish systemic-onset juvenile idiopathic arthritis from other febrile diseases

The aim of this research was to explore whether IL-18 can be a serological marker for the diagnosis of systemic-onset juvenile idiopathic arthritis (sJIA). A total of 23 sJIA patients (13 males, median age 8.2), 20 acute lymphoblastic leukemia (ALL) patients, 18 patients with severe infections (SIF), 26 Kawasaki disease (KD) patients, 18 juvenile idiopathic arthritis (JIA) patients, and 25 healthy control patients were selected for this study. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum concentrations of the S100A8, S100A9, and IL-6 proteins. The serum IL-18 levels were detected by a cytometric bead array (CBA). The serum IL-6 concentrations in various disease groups were significantly higher than that in the healthy control group. The IL-6 concentrations exhibited no significant difference between disease groups. The S100A8 level in the sJIA group was significantly higher than those of the ALL, JIA, and healthy control groups but showed no significant difference compared to the SIF and KD groups. The S100A9 serum concentration in the sJIA group was significantly higher than those in the ALL and healthy control groups and exhibited no significant difference from the SIF, KD, and JIA groups. The IL-18 level of the sJIA group was significantly higher than that of the other febrile disease groups. The IL-18 serum concentration may be used as a biological serum marker to distinguish sJIA from other febrile diseases.

Prognostic role of serum interleukin-18 in Egyptian patients with hepatitis c virus-related hepatocellular carcinoma treated by radiofrequency ablation.

Aim: The aim of this study is to identify the prognostic value of serum interleukin (IL)-18 level in hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) patients. Materials and Methods: This study was conducted in Tropical Medicine department and HCC unit in Ain Shams University Hospitals. It included 35 patients with HCV associated HCC fit for radio frequency ablation and 20 healthy control subjects. Serum IL-18 level was measured for all participants at the beginning of the study. Patients were followed-up for 1 year then serum IL-18 re-measured at the end of the follow-up period. Results: Pre-intervention serum IL-18 level was significantly higher in patients than healthy control subjects and was associated with bad clinical, laboratory or radiological prognosis. Post follow-up mean value of IL-18 level was significantly lower than pre-intervention level. Conclusion: Higher pre-intervention serum IL-18 level in HCV -related HCC patients level was associated with bad prognosis either clinically, laboratory or radiologically.

[Effect of resistance training on serum interleukin-18 and C-reactive protein in obese men]

Previous studies have reported inconsistent findings about the effect of endurance training on level of interleukin-18 [IL-18] and high-sensitivity C-reactive protein [hsCRP] in obese individuals. This study was performed to determine the effect of resistance training on serum level of IL-18 and hsCRP in obese men. In this clinical trial, eighteen obese men were randomly divided into training and control groups. After 12-hours fasting, height, weight, body mass index, body fat percent, serum level of IL-18 and hsCRP were assessed before and after training period. Resistance training protocol consisted of twelve weeks training, 3 sessions training per week, each session for 60 minutes. Mean +/- SD of IL-18 were 323.34 +/- 46.57 pg/ml and 239.43 +/- 53.75 pg/ml in training and control groups, respectively. Mean +/- SD of hsCRP was 3.83 +/- 3.65 microg/ml and 3.03 +/- 2.98 microg/ml in training and control groups, respectively. This difference was not significant. Performing resistance training for twelve weeks did not significantly reduce IL-18 and hsCRP in obese men

Serum interleukin-18 levels in patients with systemic lupus erythematosus: relation with disease activity and lupus nephritis

To further investigate the possible role of IL-18 in the pathogenesis of systemic lupus erythematosus [SLE] and development of lupus nephritis [LN], and to explore its relationship with pathological classes of LN, degree of acute renal activity and chronic damage. Forty-one SLE patients with LN, thirty-one lupus non-nephritis patients and fifteen age and sex matched healthy controls were enrolled in this study. SLE patients were subjected to disease activity assessment by SLEDAI, renal disease activity assessment by the Systemic Lupus International Collaborating Clinics [SLICC] Renal Activity Score, laboratory investigations including measurement of serum interleukin-18 using Enzyme Linked Immunosorbent Assay. Renal biopsy was obtained from LN patients and pathological classification was made according to World Health Organization [WHO] criteria. Analysis of activity and chronicity indices was done on these biopsy specimens. Serum levels of IL-18 were significantly higher in patients with LN than lupus non-nephritis patients and healthy controls [p < 0.001]. There were significant correlations between IL-18 and SLEDAI [p = 0.002], proteinuria [p = 0.027], renal activity score [p = 0.003] and activity index [p = 0.039] in patients with LN. There was no significant difference in the serum levels of IL-18 between WHO classes of LN IL-18 appears to have a pathogenic role in the development of SLE and plays a crucial role in triggering inflammation in LN. Serum IL-18 levels could be a useful biomarker to assess the activity of renal disease in SLE

[ effect of body composition and physical activity on basal levels of insulin, glucose, IL-18, IL-6 and CRP and their relationship with insulin resistance]

Obesity and physically inactive lifestyles are associated with an increased risk for developing insulin resistance. It has been confirmed that insulin resistance is a common feature in many inflammatory diseases and can be recognized with overproduced levels of markers such as IL-6, IL-18 and CRP. The aim of this study was to determine whether obesity or inactivity are stronger factors in the develop mental insulin resistance, considering insulin resistance markers such as IL-6, IL-18 and CRP. Thirty-two healthy, male students participated in the present study, age 24. 8 +/- 2.52 years, height 175.47 +/- 6.7, and weight 81.64 +/- 20.14]. Weight and body fat were measured with the body composition set and levels of exercise was determined with the PA-Rscore questionnaire. All subjects based on body fat and levels of exercise were divided into 4 groups: Active obese [n=8], active, non-obese[n=8], inactive, obese [n=8] and inactive, non obese[n=8]. To determine fasting values of IL-6, IL-18, CRP, glucose and insulin blood samples were obtained at 8 a.m. Obese subjects had higher resting levels of IL-6, IL18, CRP and insulin than lean subjects, with no significant difference between active lean and inactive lean subjects at resting levels of inflammatory markers. However there was a significant difference in the resting levels of IL-18 between active and inactive obese subjects [t=-2.51 p=0.031], and also a significant difference in resting levels of IL-6, IL18, CRP, insulin and HOMA between inactive obese with active and inactive lean subjects, IL-18 having the strongest relationship with HOMA [r=0.54 p=0.001]. Results indicated that obesity is a stronger factor than inactivity for development of insulin resistance. On the other hand, activity has anti-inflammatory effects, and hence can decrease the effects of obesity, in the development of insulin resistance

Study of IL-10 and Il-18 levels in relation to different stages of liver fibrosis in Egyptian chronic hepatitis C infected patients

Most acute and chronic liver diseases are characterized by inflammatory processes with enhanced expression of various pro-and anti-inflammatory cytokines in the liver. These cytokines are the driving force of many inflammatory liver disorders often resulting in fibrosis and cirrhosis. This work aimed to identify the role of serum IL-10 and IL-18 in the pathogenesis of chronic hepatitis C in different grades and stages of HCV patients and correlate their levels to the necroinflammatory grade and stage of fibrosis. A prospective study on [55] HCV infected patients 43 males and 12 females, their age ranged from 20 to 55 years with a mean of 41.3 year and [20] age and sex matched control [HCV-ve] from National Hepatology and Tropical Medicine Research Institute clinics, from whom consents were taken. The patients included in this study were those originally enrolled on protocol for treatment [interferon + ribavirin] where liver biopsy was required for eligibility of treatment according to the approved protocol. 5ml of blood was collected at the same day of biopsy for assessment of IL-10 and IL-18 levels in blood [ELISA technique]. Serum level of IL-18 was significantly higher in patients with chronic HCV [126.80 +/- 11.76 pg/ml] as compared to control group [45.97 +/- 5.26 pg/ml]; the level was even higher in cases with hepatocellular carcinoma [HCC]. IL-18 levels were significantly higher in patients with early fibrosis than in patients with advanced fibrosis., it was also higher in case with minimal to mild necro-inflammatory grade than in cases with moderate to severe grades, but that difference was not significant. As regards serum IL-10, the level was also higher in patients with chronic HCV [9.24 +/- 1.9 pg/ml] than control group [3.28 +/- 1.81 pg/ml]. Serum IL-10 level was significantly lower in early than advanced stages [P=0.04]. When classifying cases according to necro-inflammatory grade the IL-10 level was lower in minimal/mild cases than moderate /severe cases, but this difference wasn't statistically significant. Serum concentrations of IL-10 and IL18 could be correlated to the histopathological spoilage of the liver as they can predict the stage of fibrosis and hence can be used as indirect markers to assess the severity of liver disease in HCV infected patients. They can also be used as complementary markers in HCC patients

Endothelin-1 and Interleukin-18 with polycystic ovary syndrome

The aim of this study is to evaluate the serum level of the endothilin-1 and the interleukin-18 In patients with polycystic ovary syndrome. A Case Control Study. Ain Shams University Maternity Hospital and Ahmed Maher Teaching Hospital. 45 women will participate in the study divided to two groups. Group A [30 with Polycystic Ovarian Syndrome]. Group B [15 controls]. Patients with PCOS will be recruited from the infertility and gynecological clinics. Control subjects are healthy volunteers with a normal menstrual cycle and with no clinical or biochemical features of hyperandrogenism, thereby excluding the diagnosis of PCOS in this group. Blood Samples will be collected and examined by in-vivo enzyme immunoassay for detection of total human lnterleukin-18 and Endothelin-1 in complex biological body fluids. Results shows that the PCO cases had a higher serum Endotheline-1 level than that of the controls with statistically significant difference; [p <0.001.] and results show that the serum level of Interleukin-18 is greater in PCO patients than that of the controls with statistically significant difference; p = 0.038. PCOS induce an increase in serum IL-18 levels and the endotheline-1 concentration

Plasma concentration of osteopontin [OPN] in children with systemic lupus erythematosus: relationship with disease activity

Osteopontin [OPN] is an important bone matrix mediator found to have key roles in inflammation and immunity. OPN is a cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between T-helper 1 and T-helper 2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Overexpression of OPN has been associated with the development of the autoimmune/lymphoproliferative syndrome. The aim of our present study was to analyze the possible correlation between the plasma concentration of OPN and disease activity in children with Systemic Lupus Erythematosus [SLE]. We also investigated the correlation between plasma IL-18 and OPN concentrations to further confirm the association of OPN with disease activity. We measured the plasma concentration of OPN, and the plasma proinflammatory IL-18 concentration in 40 SLE patients with or without renal disease [RSLE group and SLE group, respectively] and in 30 sex-and age-matched controls using enzyme immunoassay. Plasma OPN concentrations were significantly higher in RSLE and SLE patients than in the controls [p=0.000 and p=0.002]. Increase in OPN concentration correlated positively and significantly with SLE disease activity index in all SLE patients [r=0.34; p=0.04]. In RSLE patients, plasma OPN concentration showed a significant positive correlation with proinflammatory cytokine IL-18 concentration [r=0.48; p=0.004]. In conclusion, The above results suggest that the production of OPN is associated with the inflammatory process and SLE development, and may serve as a potential disease marker of SLE

Association between rheumatoid arthritis activity and atherosclerosis

We assessed atherosclerosis as a risk factor in rheumatoid arthritis [RA] patients who experience excess atherosclerosis and cardiovascular risk. They were compared with osteoarthritis [OA] patients as a control group. The severity of atherosclerosis remains to be determined through carotid intima-media thickness [IMT] as a reflector for systemic atherosclerosis. The study was performed on 30 RA patients without history of cardiovascular accidents. The severity of carotid atherosclerosis was evaluated with the mean max IMT, i.e., mean of the maximal wall thickness at carotid segments. Serum level of IL-18 was measured in both RA and OA groups. Erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP] were used to measure systemic inflammation. The relationship of the carotid artery IMT with inflammatory markers was examined in RA versus OA as a control. IL-18 concentration was higher in RA versus OA and it positively correlated with IMT, p<0.05. Lipid profile was also higher in RA than OA and positively correlated with CRP, ESR and IL -18 serum level hyperlipidemia and body mass index [BMI], p<0, 05, We demonstrated an association between higher serum IL-18 level and atherosclerotic risk factors. Increased liability of atherosclerosis has the link between IL-18 and atherosclerosis. So, inflammation and cardiovascular risk factors interact to enhanced atherosclerosis in RA patients. Our findings need more evaluation in large study groups with cardiovascular risk profiles

Serum interleukin-18 levels are raised in diabetic ketoacidosis in Chinese children with type 1 diabetes mellitus.

OBJECTIVE: To investigate the role of serum interleukin (IL-18) in children with type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). DESIGN: Case-control study. SUBJECTS: Sixty-one children with T1DM including 28 with DKA and 33 without DKA and 30 age - and sex-matched healthy controls were recruited. METHODS: Serum IL-18, IL-12, and IFN-gamma levels were measured in all subjects by enzyme linked immunosorbent assay. RESULTS: Serum IL-18 levels were significantly higher in patients with DKA than those in patients without DKA (759.2 +/- 353.8 pg/mL vs. 634.9 +/- 399.7 pg/mL, P = 0.001) and healthy controls (310.0 +/- 265.3 pg/mL). The serum IL-12 and IFN-gamma levels were not different between patients and controls (277.5 +/- 207 pg/mL vs. 351.4 +/- 223.4 pg/mL, P = 0.45 and 7.02 +/- 7.53 pg/mL vs. 5.59 +/- 5.34 pg/mL, P = 0.21, respectively). CONCLUSION: Serum IL-18 levels are increased in children with type 1 diabetes mellitus and could be a predictor of diabetic ketoacidosis.

Role of pro-inflammatory cytokines, and matrix metalloprotinases in the pathogenesis of heart failure

Extracellular matrix remodeling is thought to play an important role in the progression of heart failure [HF]. Matrix metalloproteinases [MMPs] and tissue inhibitors of metalloproteinases [TIMPs] are matrix-degrading enzymes that have been demonstrated to influence left ventricular properties and serve as targets of potential anti-remodeling agents. It has been reported that MMPs concentration and activity are upregulated in the failing human heart. However, there are few reports describing the role of elevated level of circulating MMPs in severe congestive heart failure [CHF] patients. This study examined whether circulating MMPs are also related to the pathogenesis of CHF. The study involved 50 patients with severe CHF and 20 apparently healthy subjects, with matched age and sex were selected as a control group. Two Dimensional echocardiography, Doppler and colour flow mapping were done for the patients. Left ventricular dimensions [LVD] and cardiac size were measured. LV mass [LVM] was calculated from Interventricular septum [IVS], Left ventricular end diastolic dimensions [LVEDd], Left ventricular wall thickness [LVWT] and Left ventricular end systolic dimension [LVESd]. The serum levels of MMP-2, MMP-9 and TIMP-l as well as IL-18, TNF-alpha as pro-inflammatory cytokines were measured in patients with CHF and control subjects. The serum levels of MMP-2, MMP-9, TIMP-1, IL-18 and TNF-alpha were significantly higher in the CHF patients than control group. Moreover, MMP-2, MMP-9 and TIMP-1 serum levels were positively correlated with the levels of IL-8, TNF-alpha, cholesterol, triglyceride and CRP. Furthermore, MMP-2, MMP-9 andTIMP-1 were positively coffelated with LVM, LVED[d] and LVWT. We conclude that, the increasing serum levels of MMP-2, MMP-9 and TIMP-l were associated with increased LV diastolic dimensions and increased wall thickness in patients with CHF. These observations indicate that MMPs and TIMP- I serum levels may be markers for cardiac extracellular matrix degradation, a process involved in LV remodelling. These findings may open a new avenue for therapy that ameliorating heart failure especially high risk patients

Clinical Significance of Serum Interleukin-18 Concentration in the Patients with Atopic Dermatitis / 대한진단검사의학회지

BACKGROUND: Interleukin (IL)-18, a potent inducer of interferon gamma (IFN-gamma), is known to have a role in diseases involving type-2 T helper cell responses including atopic dermatitis. In this study, we aimed to determine the clinical significance of serum IL-18 level in the patients with atopic dermatitis. METHODS: Serum concentration of IL-18, IFN-gamma, IgE, and blood eosinophil were measured in the patients with atopic dermatitis and healthy control subjects, and their association with the clinical score of the disease was analysed. RESULTS: Serum concentrations of IL-18 were significantly elevated in patients with atopic dermatitis compared to the healthy controls (332 pg/mL vs 151 pg/mL, P<0.05). Serum levels of IL-18 (r=0.41, P=0.001), eosinophil (r=0.36, P=0.003), and IgE (r=0.32, P=0.009) correlated with clinical scores in the patients. Also, multiple regression analysis indicated that serum IL-18 and IgE levels were independent predictors for the clinical score of atopic dermatitis (r2=0.25, beta=0.39, P=0.001 and beta=0.32, P=0.009). CONCLUSIONS: Our results confirmed a significant correlation between the concentration of serum IL-18 and the severity of atopic dermatitis. Although serum IL-18 concentration reflects the disease severity, its usefulness as a clinical test needs to be further investigated, because its additive benefit over those of conventional blood tests is not evident so far.

Interleukin-18 and nitric oxide and gene expression of IL-18 in children with lupus nephritis

Autoimmune diseases might be caused by an imbalance of T-helper cell [Th] cytokines. Lupus nephritis [LN] is dominated by a Th1 immune response in systemic lupus erythematosus [SLE]. Interleukin-18 [IL-18] promotes polarization of the immune response towards Th1 in LN. Nitric oxide [NO] is involved in the pathogenesis of glomerulonephuitis and collagen-vascular diseases. The aim of the present study is to investigate role of IL-18 and NO in patients with LN and to study the correlation between them and Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] score and whether these two molecules are associated with renal involvement in patients with SLE. We investigated plasma concentrations of IL-18 and NO and gene expression of IL-18 was analyzed by Reverse transcription-polymerase chain reaction [RT-PCR] in 19 SLE patients with LN, [group1] and 15 SLE patients without renal involvement [group2] and 15 age- and sex-matched healthy control subjects [group3]. IL-18 and NO concentrations were measured by ELISA and colourimetric non-enzymatic assay, respectively. Plasma IL-18 and NO concentrations were significantly higher in renal group 1 than non renal group 2 and normal control group 3 [p=0.001 and 0.01 respectively]. Elevation of plasma IL-18 in renal group 1 correlated positively with SLE disease activity index and plasma NO concentration [r=0.35, p=0.0001 and r= 0.46, P=0.01, respectively], and the latter also showed a positive correlation with serum creatinine [r=0.69, P=0.001] and urea [r = 0.28, P = 0.001]. There was no significant difference in gene expressions of IL-18 in peripheral blood mononuclear cells among renal group 1, non renal group 2 and normal control group3. IL-18 is therefore suggested to play a crucial role in the inflammatory processes of renal disease in SLE. IL-18 may play a crucial role in the inflammatory process of renal disease in SLE and its measurement may be helpful for the early identification of lupus patients with LN. Elevated concentrations of circulating NO can serve as indicators of endothelial activation and/or damage, which may occur in the pathogenesis of SLE with LN

Study of soluble pro-inflammatory cytokine interleukin 18 in patients with acute coronary syndrome

Inflammatory mediators are intimately associated with the cascade of events ading to atherosclerotic plaque initiation, development, and rupture. This recognition has stimulated the evaluation of several markers of inflammation as potential tools for cardiovascular risk prediction interleukin IL-18 originally was identified as an interferon [IFN-gamma] inducing factor in Kupffer cells and macrophages. Increased IL-18 expression has been reported in human atherosclerotic plaque, mediating IFN-gamma release locally. The aim of this study is to assess the relation between serum concentrations of interleukin IL-18 and the clinical instability of coronary artery disease and to evaluate the relation between IL-18 serum levels and the extent of myocardial dysfunction. This study included forty subjects. Twenty patients with acute coronary syndrome [ten with myocardial infarction and ten with unstable angina] and ten patients with stable angina. Ten apparently healthy subjects were used as a reference group. All patients were examined and underwent ECG, diagnostic coronary angiography, some routine laboratory investigations such as [Complete blood picture, erythrocyte sedimentation rate, fasting and post- prandial blood glucose, liver function tests and renal function tests] and specific laboratory investigation as Lipid profile assessment. Measurements of specific cardiac markers: [serum levels of CK, CK- MB, LDH and qualitative determination of troponin I]. Measurement of serum interleukin-18 [IL-18] and serum high sensitivity C- reactive protein [hs -[CRP]. Plasma concentrations of IL-18 were significantly increased in the unstable angina and MI groups in comparison with the stable angina and control groups [p < 0.01]. No difference in IL-18 oncentrations were found between patients with unstable angina, and patients with Q wave MI. Plasma IL-18 concentrations significantly correlated with decreased left ventricular ejection fraction [p = 0.001]. Plasma IL-18 concentrations are increased in patients with at acute- coronary syndrome and correlate with the severity of myocardial dysfunction

Serum gamma INF inducing factor [IL18] levels in patients with chronic liver disease

Interleukin 18 [IL18] is likely to play a role in inflammatory liver disease, it is currently regarded as the primary inducer of INF gamma in inflammatory reaction, in chronic hepatitis C a significant up regulation of IL 18 in the inflammatory infiltrate has been demonstrated. The study aimed to evaluate the serum levels of IL18 in patients with chronic liver disease and to assess its role in the clinical outcome of patients with liver injury. The cohort consisted of 60 subjects age ranged from 32-65 ys, they were stratified into 4 groups; G1: 15 patients with chronic liver diseases. G2: 15 patients with liver cirrhosis G3: 15 patients with Hepatoma. G4: 15 healthy subjects serving as control Beside full routine laboratory tests. The patients were tested for autoantibodies [ANA,SMA, AMA] ,viral markers and determination of IL18 serum by ELISA. At presentation a significant increase of serum IL18 was found in all groups compared to control in addition IL18 was significantly higher in G3 than G2, furthermore it was significantly higher in G2 than G1. Moreover IL18 showed also a significant positive correlation with AST, ALT,TB,DB. in contrast a negative correlation was detected with albumin and PT It can be concluded that IL18 is likely to be involved in the pathogene-sisof human liver diseases

Evaluation of Serum Interleukin-18 levels in Helicobacter Pylori-infected peptic ulcer patients and its Association with Bacterial CagA Virulence Factor

Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide. Predominant T-helper 1 [Th1] responses with increased gamma interferon [IFN- gamma] levels have been proposed to play an important role in H. pylori-induced peptic ulcer. However, bacterial factors contributing to the initiation of Th1 polarization of H. pylori-specific immune responses have not been characterized. Comparing serum concentrations of IL-18 in H. pylori-infected peptic ulcer [PU] patients, H. pylori-infected asymptomatic [AS] carriers and healthy control group and its association with bacterial virulence factor CagA. Thirty H. pylori-infected PU patients [20 patients were positive for anti-CagA antibody and 10 patients were negative for anti-CagA antibody], 30 H. pylori-infected [AS] carriers [15 subjects with positive test for anti-CagA antibody and 15 subjects with negative test for anti-CagA antibody] and 20 healthy uninfected subjects were included in this study. Serum concentration of IL-18 was measured by ELISA method. The mean serum levels of IL-18 in PU patients [333.2 pg/ml +/- 158], was significantly higher than those found in AS [146.5 pg/ml +/- 90.1; P<0.001] and healthy control [82.2 pg/ml +/- 45.7; P<0.0001]. In both PU and AS groups, mean serum IL-18 levels in subjects with positive test for anti-CagA antibody were significantly higher than those observed in subjects with negative test for anti-CagA antibody. No significant difference was observed between serum IL-18 levels of healthy uninfected control and AS carriers with negative test for anti-CagA antibody. The results of the present study showed higher serum concentrations of IL-18 in peptic ulcer patients compared with H.Pylori carriers and healthy controls. This difference in cytokine levels may be explained by differential expression of H.Pylori CagA gene during the course of the infection

Serum interleukin-18 level and natural killer cell percentage in systemic lupus erythematosus: clinical correlation

To detect serum interleukin -18 level and natural killer cell percentage in patients with systemic lupus erythematosus and to find out their correlation with disease activity and their role in lupus renal disease. The study included 30 female patients with systemic lupus erythematosus [15 patients with lupus nephritis and 15 patients without renal disease]. 10 apparently healthy females with matched age represent the control group. All patients were subjected to full history taking, thorough clinical examination, assessment of disease activity using modified systemic lupus erythematosus disease activity index [SLEDAI], laboratory investigations especially serum interleukin-18 level, natural killer [NK] cell percentage, serum urea, serum creatinine and 24 hours urinary protein. Serum level of interleukin-18 [IL-18] was significantly increased and percentage of NK cells was significantly decreased in patients with systemic lupus erythematosus [SLE] when compared to controls. In patients with SLE, increased serum IL-18 level showed significant negative correlation with NK cell percentage while this correlation was significantly positive with SLEDAI. Serum IL-18 level was significantly higher and NK cell percentage was significantly lower in SLE patients with lupus nephritis compared to those with no renal disease. In patients with lupus nephritis, increased serum IL-18 level showed significant positive correlation to serum urea, serum creatinine and 24 hours urinary protein, while reduced percentage of NK cells showed significant negative correlation with serum creatinine. The findings of this study may indicate that increased serum IL-18 levels and reduced NK cell percentage may play a role in pathogenesis and activation of SLE and renal involvement in this disease. Further studies are recommended for IL-18 as a potential target in treatment of autoimmune diseases including SLE

Role of serum interleukin-18 in the assessment of activity of tuberculosis

This study is carried out to evaluate the role of interleukin-18 [IL-18] in the immune response against Mycobacterium tuberculosis [M. tuberculosis] and the reliability of its serum level in the assessment of tuberculous disease activity. It included 40 subjects who were classified into three groups, group I [included 20 patients with active pulmonary tuberculosis], group II [included 10 patients with active extrapulmonary tuberculosis], and group III [included 10 healthy subjects served as controls]. All subjects were investigated, before and 3 months after start of antituberculous treatment, by conventional methods to assess tuberculous disease activity [clinical features, ESR, sputum direct smear for acid fast bacilli and chest X-ray] and measurement of serum IL-18 level. In group I, 16 patients showed good response to treatment and became inactive and showed significant reduction in serum IL-18 level, while the remaining 4 patients showed poor response to treatment and still active and their serum IL-18 level did not change significantly. In group II, 9 patients showed good response to treatment and became inactive and their serum IL-18 level was reduced significantly. In conclusion, serum IL-18 plays an important role in the immune response against M. tuberculosis, as it was higher in patients than in the healthy controls. Serum IL-18 level is directly proportionate to the tuberculous disease activity and severity and it caries a prognostic value, where patients with high serum IL-18 level had good response to treatment, while patients with low serum IL-18 level had poor response to treatment

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