Intravenous immunoglobulin preparations attenuate lysolecithin-induced peripheral demyelination in mice and comprise anti-large myelin protein zero antibody.

Intravenous immunoglobulin (IVIg) has been used to treat inflammatory demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, and multifocal motor neuropathy. Despite studies demonstrating the clinical effectiveness of IVIg, the mechanisms underlying its effects remain to be elucidated in detail. Herein, we examined the effects of IVIg on lysolecithin-induced demyelination of the sciatic nerve in a mouse model. Mice -administered with IVIg 1 and 3 days post-injection (dpi) of lysolecithin -exhibited a significantly decreased demyelination area at 7 dpi. Immunoblotting analysis using two different preparations revealed that IVIg reacted with a 36-kDa membrane glycoprotein in the sciatic nerve. Subsequent analyses of peptide absorption identified the protein as a myelin protein in the peripheral nervous system (PNS) known as large myelin protein zero (L-MPZ). Moreover, injected IVIg penetrated the demyelinating lesion, leading to deposition on L-MPZ in the myelin debris. These results indicate that IVIg may modulate PNS demyelination, possibly by binding to L-MPZ on myelin debris.

Oral supplementation of a cell preparation of Enterococcus faecalis strain EC-12 stimulates superoxide dismutase production in the livers of healthy and arthritis-induced mice.

Hepatitis, a major human chronic inflammation disease, has been linked to oxidative stress, which can be initiated by radicals produced during the oxidative metabolism. Oxidative damage has been also observed in arthritis-induced mice. Here we evaluated whether supplementation of a cell preparation of Enterococcus faecalis EC-12 could induce superoxide dismutase activity and/or damage in the livers of healthy mice or mice with arthritis. In Experiment 1, both healthy and arthritis-induced mice were orally given a saline solution, or a solution with a low (0.2 mg/mouse/day) or a high (2.0 mg/mouse/day) concentration of E. faecalis EC-12 for 49 consecutive days. Manganese superoxide dismutase activity increased in E. faecalis EC-12-supplemented mice but with no arthritis. In Experiment 2, mice received orally either a saline or an E. faecalis EC-12 suspension (10 mg/kg of body weight/day) for 28 consecutive days. No changes in tissues and levels of function markers and 8-hydroxy-2'-deoxyguanosine were observed in mouse livers, inferring that E. faecalis EC-12 supplementation caused no damage. While mRNA expression of copper/zinc superoxide dismutase remained unaltered, that of manganese superoxide dismutase increased in E. faecalis EC-12 administration mice. In conclusion, at least in healthy mice, E. faecalis EC-12 supplementation stimulated manganese superoxide dismutase activity in liver tissues with no side effects.

Modification of lipid A structure and activity by the introduction of palmitoyltransferase gene to the acyltransferase-knockout mutant of Escherichia coli.

Lauroyltransferase gene (lpxL), Myristoyltransferase gene (lpxM) and palmitoyltransferase gene (crcA) of Escherichia coli BL21 were independently disrupted by the insertional mutations. The knockout mutant of two transferase genes (lpxL and crcA) produced lipid A with no lauric or palmitic acids and only a little amount of myristic acid. The mutant was susceptible to polymyxin B, but showed comparable growth with the wild-type strain at 30°C. The palmitoyltransferase gene from E. coli (crcA) or Salmonella (pagP) was amplified by PCR, cloned in pUC119, and transferred into the double-knockout mutant by transformation. The transformant contained palmitic acid in the lipid A, and recovered resistance to polymyxin B. Mass spectrometric analysis revealed that palmitic acid was linked to the hydroxyl group of 3-hydroxymyristic acid at C-2 position of proximal (reducing-end) glucosamine. LPS from the double-knockout mutant showed reduced IL-6-inducing activity to macrophage-like line cells compared to that of the wild-type strain, and the activity was only slightly restored by the introduction of palmitic acid to the lipid A. These results suggested that the introduction of one palmitic acid was enough to recover the integrity of the outer membrane, but not enough for the stimulation of macrophages.

Oral administration of Euglena gracilis Z and its carbohydrate storage substance provides survival protection against influenza virus infection in mice.

Euglena gracilis Z is a micro-algae that is used as a food or nutritional supplement. Paramylon, the carbohydrate storage substance of Euglena gracilis Z has ß-1, 3-glucan structure. Euglena gracilis Z and paramylon are reported to affect the immune system. In this study, we investigated the protective effects of Euglena gracilis Z and paramylon against influenza virus infection in mice. Euglena gracilis Z and paramylon were administered to mice as a 2% dietary mixture ad libitum. At 2 weeks after initiation of dietary administration, mice were infected intranasally with influenza virus A/PR/8/34 (H1N1). Survival rate was monitored 10 days after infection. In addition, we performed virus titer and cytokine profiles in the lung. High survival rates were observed for Euglena gracilis Z and paramylon-treated groups compared to the control group. Significantly lower virus titer in the lung was observed in the Euglena gracilis Z and paramylon-treated groups compared to the control group from day 1 after infection. Higher amount of IL-1ß, IL-6, IL-12 (p70), IFN-γ, and IL-10 was observed in the paramylon groups compared to the control group. Our data therefore reveals a novel immunoregulatory role of the Euglena gracilis Z and paramylon which provides protection against influenza virus infection.

Pulmonary TCR γδ T cells induce the early inflammation of granuloma formation by a glycolipid trehalose 6,6'-dimycolate (TDM) isolated from Mycobacterium tuberculosis.

We previously showed that formation of pulmonary granulomas in mice in response to a mycobacterial glycolipid, trehalose 6,6'-dimycolate (TDM) is due to the action of TNF-α and not of IFN-γ. However, the mechanisms of formation and maintenance of pulmonary granulomas are not yet clear. The purpose of the present study is to evaluate the mechanisms of granuloma formation by TDM at the early phase. Histological analysis showed that inflammatory cells infiltrated the murine pulmonary interstitium on day 2 after an intravenous injection with TDM as a w/o/w emulsion. Clear granuloma formation was observed on day 7 after the injection. The mRNA expression of IL-17, IFN-γ and macrophage inflammatory protein 2 was found in lung mononuclear cells at the day after TDM injection. The major IL-17-producing cells were T-cell receptor (TCR) γδ T cells expressing Vγ6. In mice depleted of γδ T cells by treatment with anti-TCR γδ monoclonal antibody, the number of TDM-induced granuloma was decreased, but the size of granuloma was not affected. Our results suggest that the mycobacterial glycolipid TDM causes activation of IL-17-producing TCR γδ T cells and stimulates chemotaxis of inflammatory cells including neutrophils in to lung.

Image quality of abdominal ultrasonography after esophagogastroduodenoscopy is preserved by using carbon dioxide insufflation: A non-inferiority test in the same subject.

Because bowel gas deteriorates the image quality of abdominal ultrasonography (AUS), it is common to perform AUS prior to esophagogastroduodenoscopy (EGD). This one-way order limits the availability of examination appointments. To evaluate whether EGD using insufflation of carbon dioxide (CO2), which is rapidly absorbed by the gastrointestinal mucosa, preserves the image quality of AUS performed subsequently, we designed a non-inferiority test in which each subject underwent AUS, EGD with CO2 insufflation, and a second AUS, in that order. All saved AUS moving images were randomized and imaging quality was evaluated at 16 organs using a four-point Likert-like scale that divides the depiction rate by 25%. Sample size was calculated to be 26 using the following: non-inferiority margin of -0.40 corresponding to depiction rate of -10%, difference of means of 0.40, common standard deviation of 1.25, power of 90%, and 1-sided α-level of 0.025. We enrolled 30 subjects. The mean and 95% confidence interval (CI) of the image quality score of all 16 organs at pre- and post-EGD AUS in the 30 subjects were 3.54 [3.48-3.60] and 3.46 [3.39-3.52], respectively. The difference in the means was 0.08 of the scores, corresponding to a 2% depiction rate. The effect size was 0.172. The image quality of post-EGD AUS was not inferior, as demonstrated by the 97.5% CI of the difference, which did not cross the non-inferiority margin of -0.40. In conclusion, the use of CO2 for insufflation in EGD does not cause much deterioration in the image quality of AUS performed subsequently. Therefore, it is permissible to perform EGD prior to AUS, which is expected to improve the efficiency of examination setup.

Potentiation of murine innate immunity by alpha-galacturonosyl-type glycosphingolipids isolated from Sphingomonas yanoikuyae and S. terrae.

Glycosphingolipids (GSLs) are components of the outer membrane of Sphingomonas species, commonly classified into two types, alpha-glucuronosyl ceramide (alpha-GlcACer) and alpha-galacturonosyl ceramide (alpha-GalACer), respectively. GSL-7 from S. yanoikuyae and GSL-13 from S. terrae, with alpha-GalACer-type structure, possess dihydrosphingosine but with a different ratio of C21cyclopropane to C20:1, while other parts remain similar. We therefore examined if this difference in the ratio of C21cyclopropane to C20:1 in the two ceramides may influence activation of, not only invariant natural killer T (iNKT) cells, but also other cells involved in innate immunity. GSL-7 with a large proportion of C21cyclopropane induced stronger activation of iNKT cells, natural killer cells, dendritic cells, and macrophages than GSL-13 with a large proportion of C20:1. The results show that a higher ratio of C21cyclopropane to C20:1 in the dihydrosphingosine molecule allows a more optimal activation of iNKT cells and other cell types.

Potent Inhibitory Effects of Quercetin on Inflammatory Responses of Collagen-Induced Arthritis in Mice.

BACKGROUND: Production of tumor necrosis factor (TNF)-α by inflammatory cells in lesions is the hallmark of the pathogenesis of rheumatoid arthritis (RA). Regulation of inflammatory responses in knee joints of patients with RA is critical for improving severe symptoms. Flavonoids have inhibitory effects on the acute and chronic inflammatory responses caused by TNF-α. The flavonoid quercetin (QUER) is one of the most prominent dietary antioxidants. OBJECTIVE: The present study investigated the preventive and therapeutic effects of QUER on inflammatory responses in collagen-induced arthritis (CIA) in mice. METHODS: Mice with CIA, a mouse model for RA, were treated with QUER orally three times a week either from the second immunization with collagen (day 21) or day 28 when symptoms of CIA had developed midway. RESULTS: In both cases, inflammation-related clinical scores of knee joints were significantly reduced by treatment with QUER. Histological analyses showed that the representative characteristics of RA, such as damage to interchondral joints, infiltration of inflammatory cells, and pannus formation, were significantly reduced by QUER treatment. Oral administration of QUER significantly decreases lipopolysaccharide (LPS)-induced TNF-α production in a dose-dependent manner. Expression of TNF- α mRNA in knee joints was decreased in QUER-treated mice, compared with those of CIA controls. CONCLUSION: These results suggest that oral administration of QUER might effectively improve symptoms of RA.

The unique tropism of Mycobacterium leprae to the nasal epithelial cells can be explained by the mammalian cell entry protein 1A.

Leprosy is a chronic infection where the skin and peripheral nervous system is invaded by Mycobacterium leprae. The infection mechanism remains unknown in part because culture methods have not been established yet for M. leprae. Mce1A protein (442 aa) is coded by mce1A (1326 bp) of M. leprae. The Mce1A homolog in Mycobacterium tuberculosis is known to be associated with M. tuberculosis epithelial cell entry, and survival and multiplication within macrophages. Studies using recombinant proteins have indicated that Mce1A of M. leprae is also associated with epithelial cell entry. This study is aimed at identifying particular sequences within Mce1A associated with M. leprae epithelial cell entry. Recombinant proteins having N-terminus and C-terminus truncations of the Mce1A region of M. leprae were created in Escherichia coli. Entry activity of latex beads, coated with these truncated proteins (r-lep37 kDa and r-lep27 kDa), into HeLa cells was observed by electron microscopy. The entry activity was preserved even when 315 bp (105 aa) and 922 bp (308 aa) was truncated from the N-terminus and C-terminus, respectively. This 316-921 bp region was divided into three sub-regions: 316-531 bp (InvX), 532-753 bp (InvY), and 754-921 bp (InvZ). Each sub-region was cloned into an AIDA vector and expressed on the surface of E. coli. Entry of these E. coli into monolayer-cultured HeLa and RPMI2650 cells was observed by electron microscopy. Only E. coli harboring the InvX sub-region exhibited cell entry. InvX was further divided into 4 domains, InvXa-InvXd, containing sequences 1-24 aa, 25-46 aa, 47-57 aa, and 58-72 aa, respectively. Recombinant E. coli, expressing each of InvXa-InvXd on the surface, were treated with antibodies against these domains, then added to monolayer cultured RPMI cells. The effectiveness of these antibodies in preventing cell entry was studied by colony counting. Entry activity was suppressed by antibodies against InvXa, InvXb, and InvXd. This suggests that these three InvX domains of Mce1A are important for M. leprae invasion into nasal epithelial cells.

Invasion of human microvascular endothelial cells by Mycobacterium leprae through Mce1A protein.

In patients with lepromatous leprosy, Mycobacterium leprae is often observed inside the human microvascular endothelial cells (HMVEC) surrounding Schwann cells (SC) at the site of lesions in the peripheral nerves. Based on this observation, it is considered that the nasal mucous may be the invasion pathway for M. leprae and HMVEC serve as an important reservoir for the bacteria before they invade SC. In light of previous research which revealed that Mce1A protein mediates bacterial invasion into nasal epithelial cells and HMVEC, we conducted a study to determine whether the invasion of M. leprae into HMVEC can be suppressed by blocking the Mce1A protein. In this study, we analyzed bacterial invasive activity by adding recombinant Escherichia coli, which express the active region (InvX:72 a.a.) of Mce1A protein on their external membrane, into cultured HMVEC, using the adhesin involved in the diffuse adherence mechanism. The number of bacteria that invaded into the cells was then measured by a colony counting method. The active region of Mce1A was divided into four sections, and hyperimmune antisera was prepared for each section for analyzing the inhibitory effect against invasion. The invasive activity was suppressed by antibodies against InvX regions 1-24 a.a., 25-46 a.a. and 58-72 a.a. This suggests that the InvX regions 1-24 a.a., 25-46 a.a. and 58-72 a.a. of Mce1A protein play an important role in the invasion of M. leprae into HMVEC and that it may be possible to suppress entry of M. leprae in HMVEC with antibodies against these regions.

Amelioration of skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice by oral administration of Agaricus blazei extracts.

We showed in a previous study that hot-water extracts of Agaricus blazei (Agaricus extracts) had anti-tumor activity to Meth A fibrosarcoma, but it remains unclear whether the Agaricus extracts ameliorate the skewed balance of type-1 T helper (Th1) and type-2 T helper (Th2) cells. We examined whether Agaricus extracts effect the skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice. When Meth A-bearing mice were given orally either Agaricus extracts or water once a day starting 5 days after tumor implantation, spleen T cells, prepared from tumor-bearing mice treated with Agaricus extracts, in response to anti-CD3 monoclonal antibody produced significantly higher levels of interferon gamma (IFN-gamma) than that of controls. The mRNA expression of IFN-gamma-inducing protein 10 and the frequency of CD69(+) or CD49d(+) cells, among activated T cells infiltrated into tumors, significantly increased in Agaricus-treated mice, compared with those of tumor-controls. In asthma-induced mice, treatment with the Agaricus extracts caused significant downregulation of OVA-specific antibody responses of IgG1 and IgE but not of IgG2a, and significantly decreased total cell numbers, levels of interleukin 5, and eosinophil numbers in bronchial alveolar lavage fluids. IFN-gamma production by anti-CD3-stimulated spleen cells, obtained from Agaricus-treated mice, significantly increased. Our results strongly suggest that oral administration of Agaricus extracts ameliorates the Th1/Th2 balance from the Th2-skewed conditions.

Suppressive effects of the flavonoids quercetin and luteolin on the accumulation of lipid rafts after signal transduction via receptors.

Quercetin (QUER) and luteolin (LUTE) are dietary flavonoids capable of regulating the production of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). However, their mechanisms of action are not fully understood. In lipopolysaccharide-triggered (LPS)-triggered signaling via Toll-like receptor 4 (TLR4), QUER and LUTE suppresses not only the degradation of the inhibitor of kappaB (IkappaB), with resultant activation of nuclear factor-kappaB (NF-kappaB), but also the phosphorylation of p38 and Akt in bone marrow-derived macrophages that have been stimulated with LPS. We report here that, in TNF-alpha-induced signaling, QUER and LUTE significantly suppressed the production of IL-6 and activation of NF-kappaB. Accumulation of lipid rafts, the initial step in the signaling pathway, was significantly inhibited when macrophages were treated with QUER or with LUTE prior to exposure to LPS. Similarly, the accumulation of lipid rafts was inhibited by the flavonoids when B cells were activated via the membrane IgM and when T cells were activated via CD3. In contrast, QUER and LUTE did not inhibit the activation of phorbol myristate acetate-induced NF-kappaB in macrophages. Our observations suggest that QUER and LUTE interact with receptors on the cell surface and suppress the accumulation of lipid rafts that occurs downstream of the activation of the receptors.

Euglena gracilis Z and its carbohydrate storage substance relieve arthritis symptoms by modulating Th17 immunity.

Euglena gracilis Z is a microorganism classified as a microalga and is used as a food or nutritional supplement. Paramylon, the carbohydrate storage substance of E. gracilis Z, is reported to affect the immunological system. This study evaluated the symptom-relieving effects of E. gracilis Z and paramylon in rheumatoid arthritis in a collagen-induced arthritis mouse model. The efficacy of both substances was assessed based on clinical arthritis signs, as well as cytokine (interleukin [IL]-17, IL-6, and interferon [IFN]-γ) levels in lymphoid tissues. Additionally, the knee joints were harvested and histopathologically examined. The results showed that both substances reduced the transitional changes in the visual assessment score of arthritis symptoms compared with those in the control group, indicating their symptom-relieving effects on rheumatoid arthritis. Furthermore, E. gracilis Z and paramylon significantly reduced the secretion of the cytokines, IL-17, IL-6, and IFN-γ. The histopathological examination of the control group revealed edema, inflammation, cell hyperplasia, granulation tissue formation, fibrosis, and exudate in the synovial membrane, as well as pannus formation and articular cartilage destruction in the femoral trochlear groove. These changes were suppressed in both treatment groups. Particularly, the E. gracilis Z group showed no edema, inflammation, and fibrosis of the synovial membrane, or pannus formation and destruction of articular cartilage in the femoral trochlear groove. Furthermore, E. gracilis Z and paramylon exhibited symptom-relieving effects on rheumatoid arthritis and suppressed the secretion of cytokines IL-17, IL-6, and IFN-γ. These effects were likely mediated by the regulatory activities of E. gracilis Z and paramylon on Th17 immunity. In addition, the symptom-relieving effects of both substances were comparable, which suggests that paramylon is the active component of Euglena gracilis Z.

Morphometrical and Morphological Alterations of Human Leukocytes Exposed to 1.8 GHz Electromagnetic Radiations: In Vitro Protective Effects Induced by Polyphenols.

BACKGROUND: Our recent findings have demonstrated that electromagnetic radiations (EMR) (1.8 GHz radiofrequency) are able to in vitro induce morphometrical and morphological modifications of human leukocytes from normal donors. METHODS: In view of the evidence that polyphenols exert many beneficial effects on plants, animals and humans, leukocytes from human peripheral blood were pre-treated for 1 h with two polyphenol preparations from red grape before EMR exposure (1.8 GHz). RESULTS: Our data will show that polyphenol pre-treatment reverts to normality the morphology of irradiated leukocytes in comparison to irradiated cells only. Conversely, leukocyte morphometry seems to be not affected by this treatment. CONCLUSION: Here, we demonstrate that polyphenols are also able to normalize leukocyte morphology per se altered before as well as after irradiation. Finally, a working hypothesis aimed at clarifying the protective mechanisms exerted by polyphenols on irradiated leukocytes will be illustrated.

Does high mobility group 1 protein function as a late mediator for LPS- or TNF-induced shock in galactosamine-sensitized mice?

The role of high mobility group-1 protein (HMG-1) in LPS- and TNF-alpha-induced lethal shock in galactosamine (GalN)-sensitized mice was investigated. No detectable HMG-1 levels were observed by immunoblotting analysis in plasma from untreated or GalN-sensitized BALB/c mice 5 h after LPS injection, although significant levels of HMG-1 were detected in plasma 6 h after the challenge. All GalN-sensitized BALB/c but not BALB/lps(d) mice succumbed by 6 h after LPS injection. When GalN-sensitized mice were injected with TNF-alpha, the presence of HMG-1 was seen at 5.5 h in plasma of BALB/c mice and at 6 h in BALB/lps(d) mice, although almost all GalN-sensitized BALB/c mice died by 6 h after challenge. The time-dependent phenomenon correlated with elevated serum aspartate aminotransferase (AST) levels and the appearance of apoptotic cells in livers. Administration of pooled plasma, equivalent to approximately 200 microg recombinant murine HMG-1, taken from mice on the verge of near death, did not result in induction of lethal shock in GalN-sensitized mice. Taken together with the late appearance of HMG-1 in moribund mice, these data suggest that HMG-1 does not decisively contribute to lethality in the GalN sensitization model.

Crow-Fukase syndrome associated with high-output heart failure.

A 64-year-old woman was admitted with systemic edema and exertional dyspnea. High-output heart failure was diagnosed by right heart catheterization and she was treated with diuretics. After 3 weeks, her symptoms disappeared but a high cardiac output state persisted. A diagnosis of Crow-Fukase syndrome was made based on the presence of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. Her serum vascular endothelial growth factor (VEGF) level was markedly elevated after recovery from heart failure. We suspect that an elevated VEGF level and a high cardiac output state may play a role in the pathogenesis of heart failure in Crow-Fukase syndrome.

Remarkable improvement of myocardial metaiodobenzylguanidine uptake after surgery in a patient with pheochromocytoma-a case report.

A patient with pheochromocytoma showed remarkable improvement of myocardial metaiodobenzylguanidine (MIBG) uptake within a short time after surgical resection of the tumor. Myocardial MIBG findings in this case may contribute to an interpretation of the kinetics of MIBG in the human heart.

Electrical and mechanical alternans during percutaneous transluminal coronary angioplasty in a patient with acute myocardial infarction--a case report.

The authors report a rare type of cardiac alternans during percutaneous transluminal coronary angioplasty (PTCA) in a patient with acute myocardial infarction. Not only ST segment but also QRS alternans were observed on electrocardiogram and were accompanied by mechanical alternans. The mechanism of these unusual findings is briefly discussed.

Potential use of dietary natural products, especially polyphenols, for improving type-1 allergic symptoms.

Type-1 allergic diseases consist of two phases. An inductive phase comprises IgE formation to allergens based on the immune system being biased to predominant T-helper type 2 responses. In a triggering phase allergic symptoms are triggered due to a robust secretion of mediators from mast cells and other cells after re-exposure to the same allergen. Various polyphenols, found in foods and plant sources, have potent anti-allergic activities that have been shown in different disease models and in human clinical trials. The present review summarizes the recent findings and progress in the research about polyphenols and natural products, and their role in allergic diseases. Intake of representative polyphenols (flavones, flavone-3-ols, catechins, anthocyanidins, flavanones, procyanidins, and resveratrol) can improve a skewed Th1/Th2 balance and suppress antigen-specific IgE antibody formation. Oral administration of fermented grape foods (FGF), one example of natural products fermented by lactic acid bacteria, is effective for decreasing allergic symptoms in the effector phase. Inhibitory mechanisms of polyphenols are also discussed.

Immunomodulating and anti-allergic effects of Negroamaro and Koshu Vitis vinifera fermented grape marc (FGM).

Polyphenols contained in FGM from Negroamaro (N) and Koshu (K) Vitis vinifera have been shown to exhibit several immunomodulating activities. For instance, mice affected by experimental colitis when administered with K-FGM showed an attenuation of the inflammatory process. In murine asthma, K-FGM reduced IgE production and eosinophil number in bronchial alveolar lavage fluid. In vitro, both N- and K-FGM were able to induce T regulatory cells in terms of Foxp-3 molecule expression and release of interleukin-10. In another set of experiments both N- and K-FGM were able to balance rate of proliferation/apoptosis/necrosis of normal human peripheral lymphocytes, thus indicating the property of these compounds to maintain immune homeostatic mechanisms in the host. On the other hand, N- and K-FGM inhibited human basophil degranulation, thus, confirming our previous results obtained with rat basophilic leukemia cells. Finally, N- and K-FGM also decreased oxidative burst of human polymorphonuclear cells and monocytes.Taken together, these findings imply the potential clinical usefulness of FGM administration in inflammatory/allergic conditions, such as chronic asthma.