Iranian journal of immunology
Volume:8 Issue: 3, Summer 2011

Gene association studies are less appealing in cancer compared to autoimmune diseases.Complexity, heterogeneity, variation in histological types, age at onset, short survival,and acute versus chronic conditions are cancer related factors which are different froman organ specific autoimmune disease, such as Grave’s disease, on which a large bodyof multicentre data is accumulated. For years the focus of attention was on diversity andpolymorphism of major histocompatibility complex in respect to human diseasesspecially the autoimmune diseases, but in recent years, access to other human genesequences prompted investigators to focus on genes encoding the immune regulatoryproteins such as the co-stimulatory, adhesion molecules, cytokines and chemokines andtheir receptors. Among them, CTLA4 (CD152) has been in the centre of attention for itspivotal role in autoimmunity and cancer. Although not fully understood, CTLA4 withno doubt plays an important role in the maintenance of the immune response by itsexpression on activated and regulatory T cells. CTLA4 (Gene ID:1493, MIMnumber:123890) has many variants and polymorphic forms, some present in regulatorypositions, some in 3' UTR and the most important one in the leader sequence (+49 A/G).As a pivotal regulatory element of the immune responses magnitude, CTLA4 could beconsidered as a two-blade knife, for which only the optimal expression ensures aneffective, but at the same time, safe immune response. It can accordingly be speculatedthat CTLA4 alleles associated with extraordinary expression could make a person moresusceptible to tumor growth and/or progression. On the other hand, alleles associatedwith a compromised CTLA4 expression/function may accelerate the formation and/ormanifestation of inflammatory autoimmune disorder. I hypothesized a spectrum of thefunctional dichotomy of CTLA4 SNPs diverging from autoimmunity to cancer. Toexamine these hypotheses, results from previously published investigations on CTLA4polymorphisms together with the work done by our own group are discussed in details.Because the most published data are about the polymorphism at position +49, Iconcentrated on this position; however the data regarding other SNPs are also includedfor comparison. To support the significance of CTLA4 gene variation in these twomajor human diseases evidences from organ transplantation are also included. As

A β-mercaptoethnol (β-ME)-treated promastigote antigen of L. donovaniwas successfully employed in direct agglutination test (DAT) for the diagnosis ofvisceral leishmaniasis (VL). The β-ME-treated antigen was furtherincorporated into an enzyme-linked immunosorbent assay set-up (β-ME ELISA) andevaluated for VL diagnosis against outcome of reference freeze-dried DAT (FD-DAT)and rK39 strip test (RKT) commercial kits. Two-hundred and ninety-two serafrom patients with high VL suspicion of whom 105 had confirmed L. donovaniinfection were tested. Relatively higher sensitivities of 93.3% (95% CI: 88.4-98.2) and 92.4% (95% CI: 87.3-97.5) were determined for β-ME ELISA and FD-DATas compared to 83.8% (95% CI: 76.7-90.8) for RKT. Of 73 VL sera that scoredmaximum absorbance values (>0.81) in β-ME ELISA, 66 (90.4%) tested at the highestagglutination titres (>1:51200) in FD-DAT as did 56 (76.7%) also at comparablereaction intensities (3 + colour intensity) in RKT. Compared with FD-DAT (94.7%,95% CI: 91.5-97.9) or RKT (93.0%, 95% CI: 89.3-96.6), lower specificity wasestimated for β-ME ELISA (90.4%, 95% CI: 86.1-94.6). Based both on positive andnegative microscopy for L. donovani in organ aspirates of all VL suspects enrolled(292), significantly higher correlation (p<0.01, 0.919) was established between β-MEELISA and FD-DAT than between β-ME ELISA and RKT (p<0.01, 0.824). Taking intocalculation the combined estimates of sensitivity, specificity, positive and negativepredictive values, higher agreement (94.8%) was determined between total performanceof β-ME ELISA and FD-DAT than between that of β-ME ELISA and RKT (90.7%). Based on results and merits discussed, we recommend application of thisβ-ME ELISA both for diagnosis of VL at laboratory level and confirmation of resultsobtained with DAT or RKT in the field.

A number of medicinal plants have been used to treat variousimmunological diseases. Nitric oxide (NO) has an important regulatory role in thevarious types of inflammatory processes. To investigate the NO modulatoryactivity of the extracts of several medicinal plants native to Iran includingDracocephalum kotschyi, Linum persicum, Dionysia termeana, Salvia mirzayanii,Ferulago angulata and Euphorbia cheiradenia. The methanolic extracts ofthe plants were prepared and examined for their effects on the NO production bylipopolysaccharide-stimulated mouse macrophages. The level of TNF-α and IL-1β proinflammatorycytokines in the macrophage culture were detected using enzyme-linkedimmunosorbent assay. All the extracts at concentration of 50 μg/mldemonstrated a significant decrease in NO production (p<0.001) after a 24-hourtreatment. This inhibitory effect was also seen after 48 hours. Among the extracts, L.persicum was the strongest extract in reducing the NO production at 1 μg/ml after both24 and 48-hours (nearly 100% inhibition, p<0.001). S. mirzayanii extract with 66.2 ±8% inhibition at 50 μg/ml, showed the mildest effects in 48 hour culture. In cytokinerelease determination, the extract of L. persicum significantly inhibited both TNF-α andIL-1β cytokines production by stimulated macrophages (p<0.001). D. kotschyi, D.termeana and F. angulata decreased secretion of IL-1β from the cells. These results indicate the presence of anti-inflammatory and macrophage inhibitorysubstances in these plants.

Bone resorption is one of the main features of inflammatory periapicallesions and is mainly mediated by interleukin-1 beta (IL-1β), tumor necrosis factoralpha(TNF-α) and prostaglandin-E2 (PGE2). Recent investigations of these lesionsrevealed that pharmacological modulation may be possible. The aim of thisstudy was to evaluate the effect of Ibuprofen on IL-1β, TNF-α and PGE2 levels inperiapical exudates and compare the results with a group of placebo control. Thirty patients with non vital teeth and radiographic lesions were divided into twogroups of case and control according to their entrance to the study. Periapical exudateswere taken from root canals using absorbent paper points and followed by 400 mgIbuprofen and placebo prescribed one tablet every 6 hour for three days and in thefourth day second samples were taken, then final cleaning, shaping and obturation of thecanals were completed. IL-1β, TNF-α and PGE2 levels were determined by enzymelinkedimmunosorbent assays (ELISA). Data were analyzed using paired t-test andstudent's t-test. The results showed that PGE2 levels were decreasedsignificantly in the case group to 86.92 ± 72.42 Pg/ml following Ibuprofen treatmentcomparing with the pre-treatment (164.96 ± 12.255 Pg/ml) (p=0.02) and placebo group(154.2 ± 97.13 Pg/ml) (p=0.001). But there were no significant differences in IL-1β andTNF-α level between the two groups and in each group before and after treatment. The data indicate that Ibuprofen, as a non-steroidal anti-inflammatory drug(NSAID), can be used to block PGE2 release, enhance healing of inflammatoryperiapical lesions and possibly to inhibit bone resorption.

Patients with ulcerative colitis are at increased risk of inflammation.Interleukin 23 (IL-23) is a newly identified cytokine with increased expression ininflamed biopsies of colon mucosa in patients with Crohn's disease; however, there isinconsistent evidence on its role in ulcerative colitis. We aimed to compareserum IL-23 level in patients with ulcerative colitis and normal controls and determineif serum IL-23 level increases with the severity of disease according to endoscopicfindings. We quantified serum IL-23 levels from 60 patients with ulcerativecolitis and 20 control individuals. All patients underwent endoscopic procedure todefine the severity of disease. Patients were then stratified into 2 groups of "Mild" and"Severe" according to the endoscopic findings. For comparison of serum IL-23levels, Platelet count, ESR and CRP between the groups, Mann-Whitney U test andindependent sample t test were employed, as appropriate. Pearson’s and spearmanscorrelation tests were employed to test the association of IL-23 with platelet count, CRPand ESR in patients. Our findings showed that serum IL-23 levels were increased inpatients with ulcerative colitis compared to normal control. Moreover, patients in"Severe" group had higher serum IL-23 levels and ESR compared with those in "Mild"group. There was no significant sexual dimorphism in any of studied variables. We suggest that IL-23 plays an important role in the pathogenesis ofulcerative colitis and is a marker of disease activity in these patients.