Macrophage plasticity, polarization, and function in health and disease.

Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF, and produce pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, IL-12, IL-23, and TNF-α; and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-ß. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation-associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF-α, IL-1ß, IL-12, and IL-23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL-10 and TGF-ß to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti-microbial defense, anti-tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.

Therapeutic Aspects of Squill; An Evidence-Based Review.

From ancient times, medicinal plants have been usually utilized to treat many disorders, but today, interest in these herbs is again aroused, because of their fewer side effects and low-cost. In traditional medicine, for many diseases, various medicinal herbs have been suggested so far. Drimia maritime, also named squill, is an important medicinal plant for the treatment of many diseases, especially respiratory diseases. In the current evidence-based study, we conducted a review of the general characteristics, ingredients, administration form, and side effects of squill in traditional medicine. For this purpose, traditional Persian medicine literatures and electronic databases were examined including PubMed, Scopus, and Google Scholar. Many compounds are isolated from D.maritima, including scillaren, scillirubroside, scillarenin, and bufadienolide glycosides. Oxymel is the most commonly used form of squill for various diseases, especially respiratory diseases. Besides, squill has been used in the treatment of cardiovascular, digestive, and dermatological disorders, it is also used against various cancer cells for its antioxidant and cytotoxic properties. Moreover, there is relatively reliable evidence of its benefits for bacterial and helminthic infections, rheumatism, edema, gout, abortion induction, healing of wounds and urine induction. It seems that supplementary studies are required to explore the bioactive agents and their effective mechanisms.

Investigation of the Association Between Carotid Artery Intima-Media Thickness (IMT) and Cardiac Risk Factors in Patients with Systemic Lupus Erythematosus.

BACKGROUND: The relationship between SLE and traditional risk factors for cardiovascular events was evaluated. METHODS: The data regarding sixty patients with SLE and 30 healthy controls (age and sex matched) were gathered using SLEDAI forms. Venous blood (10mL) from all the participants was examined for hs-CRP, homocysteine, VCAM1, CBC, anti-DNA antibody, C3, C4, low-density lipoprotein (LDL), cholesterol, FBS and triglyceride. The IMT of carotid arteries was determined bilaterally by ultrasound. Other measurements included insulin levels via Elisa (Linco/Millipore Corp) and the HOMA-IR index for insulin resistance. RESULTS: The mean age (in years) in the test and control groups was 28.8±10.3 (18-52) and 33.8±9.13 (18-48), respectively. The average IMT in the test group was directly related to serum levels of VCAM1 (p<0.001), homocysteine (p<0.001), cholesterol (p<0.009), LDL (p<0.001), TG (p<0.001), and FPG (p=0.004). The association between other risk factors, insulin resistance, carotid IMT and SLEDAI, was nonexistent. Mean insulin and insulin resistance levels in all the participants were 0.43±2.06 µU/mL and 0.09±0.44, respectively. There was no significant difference between the test and control groups regarding serum insulin and insulin resistance levels (p=0.42 and p=0.9, respectively). None of the risk factors, such as hsCRP, VCAM1, or homocysteine, were shown to be related to insulin resistance (p=0.6, p=0.6, p=0.09, respectively). CONCLUSION: Our findings did not show an increase in the prevalence of atherosclerosis in patients with SLE. There was no association between IMT and insulin resistance. However, the former was associated with FPG, total cholesterol, LDL, TG, homocystein and VCAM1.

Relationship Between Polymorphisms of Interleukin-1 Receptor Antagonist (IL-1Ra) Genes and Susceptibility to Systemic Lupus Erythematosus in Iranian Population.

OBJECTIVES: Interleukin (IL)-1 has a major role in cell destruction and inflammation. IL-1 receptor antagonist (IL-1RN or IL-1Ra) is a natural anti-inflammatory molecule that blocks IL-1. We intended to determine whether IL-1RN or IL-1Ra variable number tandem repeat (VNTR) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) in a series of patients in the Northeastern part of Iran. METHODS: Genomic DNA was extracted from the whole blood of 104 SLE patients and 209 subjects without SLE as a control group. The control group was matched for age and gender with SLE patients. Then, genomic DNA was genotyped by polymerase chain reaction (PCR) method for a length polymorphism in intron 2 of the IL-1RN gene. RESULTS: Of five alleles, only allele 4 of IL-1RN had a higher frequency in healthy subjects (2.4%) compared to SLE patients (0), with a statistically significant difference (P= 0.03). Eleven kinds of polymorphisms of IL-1RN were found including 1/1, 1/2, 2/2, 3/3, 1/3, 3/5, 2/3, 2/5, 1/5, 4/4 and 1/4 in both groups. In genotype frequency, there was no statistically significant difference regarding gene polymorphism kinds between the two groups (P= 0.29). CONCLUSION: Alleles 4 of IL-1RN may have a protective role against SLE susceptibility. However, SLE was not associated with any of the 11 kinds of genotype IL1-RN gene polymorphisms studied here.

The effect of natural adjuvants on tracheal responsiveness and cell count in lung lavage of sensitized guinea pigs.

BACKGROUND AND OBJECTIVE: Airway inflammation is a well-characterized pathological feature of asthma. The effects of two natural adjuvants on lungs of sensitized guinea pigs were examined. METHODS: The responses of guinea pig tracheal chains, WBC, differential WBC in lung lavage and IL-4 and interferon (IFN)-gamma levels in serum were examined in control guinea pigs and four treatment groups, including sensitized animals (S) and sensitized animals treated with the adjuvants PC (S + PC), G2 (S + G2) or both adjuvants (S + PCG2) (n = 6). Animals were sensitized by injection and inhalation of ovalbumin. RESULTS: Tracheal responsiveness to methacholine (concentration of methacholine causing 50% of maximum contraction), WBC, eosinophil, neutrophil and basophil numbers were increased and lymphocyte numbers were decreased in lung lavage of sensitized animals compared with the control group (P < 0.01 to P < 0.001). However, G2 adjuvant and the combination of G2 and PC adjuvants caused a significant reduction in tracheal responsiveness (P < 0.01 and P < 0.001, respectively). In addition both adjuvants prevented changes in WBC (P < 0.001 for both). Both adjuvants and the combination prevented changes in eosinophil, neutrophil and basophil numbers in lung lavage of sensitized animals (P < 0.05 to P < 0.001). The adjuvants also prevented changes in IL-4 but increased IFN-gamma levels in all treatment groups compared with group S (P < 0.001 for all cases). CONCLUSIONS: These results indicate that the two natural adjuvants (especially G2 adjuvant) and their combination have therapeutic effects, with reduction in tracheal responsiveness and WBC in lung lavage of sensitized guinea pigs.

Interleukin-6 production by cultured peripheral blood monocytes before and after stimulation by E. coli lipopolysaccharide in Iranian patients with aggressive periodontitis.

BACKGROUND: It has been suggested that hyper-responsiveness of monocytes to the products of dental plaque, especially the endotoxin of Gram-negative bacteria and the secretion of high levels of pro-inflammatory cytokines, may have a role in the pathogenesis of aggressive periodontitis (AP). To investigate this possibility, IL-6 production by cultured peripheral blood monocytes before and after stimulation by E. coli lipopolysaccharide (LPS) in AP patients was evaluated. MATERIAL/METHODS: Fifteen patients with AP were compared with 15 periodontally healthy controls in a case control study. Monocytes were obtained from peripheral blood samples and cultured. The reaction of monocytes was studied by their IL-6 production using ELISA before and six hours after stimulation by 0.1 microg/ml E. col. LPS. The Wilcoxon and Mann-Whitney U tests were used to compare the groups. RESULTS: There was no significant difference in IL-6 production levels before LPS stimulation between patients and controls. Upon LPS stimulation, IL-6 levels increased in both the patient and control groups compared with their IL-6 levels before stimulation. IL-6 production after LPS stimulation in the patients was higher than controls, but this was not statistically significant. However, the increase in IL-6 production as a result of LPS stimulation was significantly higher in patients than in controls. CONCLUSIONS: Increased monocyte responsiveness may play a potential role in the pathogenesis of AP. However, whether this is an intrinsic characteristic of the monocyte/macrophage cells of AP patients or just a priming effect as a result of the periodontal disease remains to be investigated.