Iranian journal of immunology
Volume:7 Issue: 2, Spring 2010

Immunomodulation using medicinal plants provides an alternative to conventional chemotherapy for several diseases, especially when suppression of inflammation is desired.The "Canon of Medicine", the epochal work of Avicenna, the great Persian scientist ofthe middle ages, provides comprehensive information about medicinal plants whichused to cure inflammatory illnesses in traditional Iranian medicine. Taking into considerationthat the mechanisms of damage in these illnesses are mediated by immune responses,it is reasonable to assume that the plants used for such diseases may suppressthe immune responses and the resultant inflammation. In Iran, because of great diversityof climate and geographical conditions, numerous varieties of plants grow and at least1000 species are recorded as medicinal plants. Many of these plants such as Punicagranatum, Glycyrrhiza glabra, Foeniculum vulgare and Polygonum species prescribedby ancient Iranian physicians have been shown to possess anti-inflammatory and immunomodulatory effects. In recent literature, different species of native medicinal plantssuch as Stachys obtusicrena, Salvia mirzayanii, Echium amoenum, Dracocephalumkotschyi and Linum persicum have been shown to have appreciable anti-inflammatoryand immunomodulatory effects including inhibitory effects on lymphocyte activation,suppression of cellular and humoral immunity and induction of apoptosis. This reviewfocuses on plants that are used in Iranian traditional medicine and have been reported toact as immunoinhibitory agents.

Dendritic cells (DCs) play a central role in the initiation and expansion of T cell mediated immune responses with potential immunotherapy application. The compounds which have the ability to induce immunomodulatory effects on DCs may be employed for the treatment of immunopathologic conditions such as autoimmune diseases. The aim of this study was to investigate the in vivo effects of calcitriol (active form of vitamin D3) on DCs. 0.1 microgram calcitriol was injectedintra-peritoneally into C57BL/6 mice every other day within 3 weeks, and spleenDCs were extracted by magnetic beads. The phenotypic and functional properties ofDCs were studied by flow cytometry and mixed lymphocyte reaction (MLR), respectively. The expression of CD86 and MHC II, as maturation markers andcostimulatory molecules were significantly decreased (p=0.028 and p=0.047, respectively)while CD11b expression, as a marker of mice myeloid DCs which mostly inducesTh2 cytokine profile, was significantly increased (p=0.011). Allogeneic T cellstimulation in MLR was also significantly inhibited in comparison with the controlgroups (p<0.05). Our data indicate that in vivo calcitriol administrationinhibits maturation and activation of DCs in the same manner as in vitro conditions.

Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy. In this study, we compared tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG oligonucleotides in inducing dendritic cell maturation. We generated immature dendritic cells with GM-CSF in combination with IL-4 from peripheral blood mononuclear adherent cells and used tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG for the induction of dendritic cell maturation. CD83 maturation marker on the dendritic cells was analyzed by flowcytometry after 7 days. In addition, mixed leukocyte reaction between dendritic cells and T cells was performed by MTT proliferation assay. Flow cytometry results demonstrated a comparable high level of CD83 expression on the mature dendritic cells generated by TNF-α, CpG, Poly I:C, and LPS treatment of the immature dendritic cells. However, a significantly poorer proliferation of lymphocytes cocultured with the Poly I:C-treated DCs was observed compared to the CpG-treated DCs in mixed leukocyte reaction (p=0.026). Conversely, a significantly stronger proliferation of lymphocytes was observed when cocultured with TNF-α-treated DCs compared to the LPS-treated DCs (p=0.025). Our results indicated thatall of studied maturation inducing factors can be used in DC maturation but TNF-α andCpG were the preferred in vitro maturation factors. It is concluded that maturation of dendritic cells by CpG motif and TNF-α can be used to regulate immune responses.

The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). We investigated the HLACand HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes toevaluate whether these genes and molecules could influence Ankylosing spondylitis(AS) susceptibility, alone or in combination. We typed 40 AS patients and 40normal controls for HLA-C asn80 (group 1) and HLA-C lys80 (group 2), HLA-BBw4thero, HLA-B Bw4iso and HLA-A Bw4 alleles by PCR-SSP method. We also assessedthe expression of KIR2DL1/2DS1, KIR2DL2/2DL3, KIR3DL1 and KIR2DS4 byflow cytometry. The Pearson chi-square or Fisher exact test was performed for statisticalanalysis. The frequency of HLA-B Bw4iso but not HLA-B Bw4thero andHLA-A Bw4, ligand for the inhibitory KIR3DL1, was significantly reduced in AS patientsas compared with controls (p<0.01). No significant differences were observed ingene carrier frequencies of HLA-C group 1 and 2 between AS and controls. Althoughno differences were found in the expression of KIR receptors between AS and normalsubjects, we found that expression of KIR3DL1 in the presence of HLA Bw4-Biso genewas reduced in patients with AS compared to healthy controls (p<0.009). We conclude that HLA-B Bw4iso, the ligand of inhibitory KIR3DL1, with and without the expression of KIR3DL1 might be involved in protection against AS. Our resultssuggest that besides the HLA and KIR genotype, expression levels of KIRs may be involved in the pathogenesis of AS disease

Previous studies imply that IL-1 and IL-8 gene variations may play a crucial role in the genetic predisposition to different gastric disorders upon H. pylori infection. The aim of this study was to determine the potential association between the prevalence of certain polymorphic sites and the risk of gastric disorders inIranian population. One hundred and forty three unrelated individuals withdifferent gastric disorders and 374 normal individuals with no gastric disorders and witha negative serology test for H. pylori (control group) were studied for the associationbetween IL-1β (+3953 C/T) and IL-8 (-251 A/T) gene polymorphisms and H. pylorimediated gastritis and gastric ulcer. An analysis of genotype frequency for these genes was performed using RFLP-PCR. Based on the data obtained from culture and pathologic findings, the patients were classified into three subpopulations: H pylori+non-ulcerative gastritis+, H. pylori+ ulcerative gastritis+ and H. pylori- non-ulcerativegastritis+. A significantly higher frequency of TT genotype (p=0.02) in IL-1β +3953 inH. pylori+ ulcerative gastritis+ was revealed compared to the control group. There wereno significant differences among other subpopulations. No significant differences in alleleand genotype frequencies of IL-8 (-251A/T) were found among the patients. The data suggest that TT genotype in IL-1β +3953 may be a major contributing genetic risk factor for H. pylori induced gastric ulcer. Moreover, the role of other bacterial and host response factors, such as bacterial adherence peptides, host chemokines, and genes involved in gastric acid secretion, must be further investigated in different ethnic populations.

Atherosclerosis is an inflammatory and multifactorial disease، with a high prevalence rate in Pakistan. To find a relation between serum IL-4 and IgElevels with oxidized LDL in atherosclerosis. In this observational، cross sectionalstudy 99 male patients، between forty and sixty years of age، with a history ofischemic heart disease (IHD) and established atherosclerotic plaques on angiographywere recruited. The study was completed within three years (Jan 2007 to Jan 2009). One hundred and one age and gender matched healthy subjects with no known history of IHD were also recruited. All the study participants were non-diabetics. Serum IL-4، IgEand oxidized LDL (ox-LDL) levels were measured by quantitative ELISA technique. Serum IL-4 levels were generally undetectable or very low، but were higher inthe patient group compared to the control subjects. Similarly، oxidized LDL and serumIgE levels were also increased in the patient group compared to the control، but the differences were not statistically significant. Our study could not detect any relationship between IL-4 and IgE levels with LDL oxidation in atherosclerosis.

Anti-ganglioside antibody assays are widely used for diagnosis of autoimmune peripheral neuropathies. This study aimed to determine serum levels of anti-ganglioside antibodies in children with Guillain-Barre syndrome by immunoblotting technique and compare the results with those obtained by ELISA method. In this investigation, 50 children with Guillain-Barre syndrome (GBS) who were admitted from July 2006 to July 2008, to Tabriz Children’s hospital in the northwest of Iran were studied. 30 children admitted for various other reasons than GBS were randomly selected as a control group. The levels of anti-ganglioside antibodies in serum were measured by ELISA and immunoblotting methods using commercial kits. Anti-ganglioside antibodies (IgG) were detected in 16 (32%) GBS patients and in 1 (3.3%) control using ELISA assay. However, by employing immunoblotting technique, antibodies against seven gangliosides were found positive in 28 (56%) GBS patients and none in the control group. The sensitivities of immunoblotting and ELISA methods were 56% and 32% and their specificities were 100% and 97%, respectively (p<0.001). According to the clinical criteria of GBS, the specificity and sensitivity of immunoblotting was better than those of ELISA. It is important to notice that the immunoblotting method is able to measure the seven types of antibodies (GM1, GM2,GM3, GD1a, GD1b, GT1b, and GQ1b) simultaneously and it is an easy, routine methodwith a lower cost.

The relationship of inflammatory cytokines with anxiety and depression has been reported, but their role in diabetic patients has not been fully elucidated. We examined whether an association between prevalence of anxiety and depression in Omani type-2 diabetic patients (n=30) and the levels of inflammatory markers such as IL-1β, TNF-α, IFN-γ and C-reactive protein (CRP) exists. Symptoms of anxiety and depression were screened using the Hospital Anxiety and Depression Scale (HADS) through self-rated questionnaires. IL-1β, TNF-α, IFN-γ, CRP, anti-TPO and anti-GAD65 antibodies were measured in patients'' sera using commerciallyavailable ELISA assays. In Omani type 2 diabetic patients, high prevalence ofanxiety and depression along with high levels of inflammatory markers were detected.However, no correlation was observed between inflammatory markers and anxiety ordepression. These results indicate that Omani type 2 diabetic patients areat great risk for developing anxiety and depression. Therefore, these complications needmore care and attention. There was no association between scores of anxiety and depression with the levels of inflammatory cytokines. This may need to be elucidated in alarger cohort of patients.