Effervescent Glutamine Formulation Improves the Beneficial Effects of Antiretroviral Therapies on Immune Function in HIV/AIDS Carrier Patients.

The impact of oral supplementation with an effervescent glutamine formulation on the beneficial effects of antiretroviral therapies was evaluated in people living with HIV/AIDS. For this purpose, 12 HIV/AIDS carrier patients with CD4+ T cell counts <500, and who had received the same antiretroviral therapy for at least 1 year before starting this investigation were selected. The patients were required to dissolve the effervescent glutamine formulation (supplied in sachets) in water immediately before oral ingestion (12.4 g), once a day, after lunch or after dinner during 30 days. CD4+ T cell counts, complete blood cell counts, serum cytokines, and amino acids levels were quantified; biochemical and toxicological measurements were performed. The numbers of CD4+ T cells were increased (P < .05), and the serum C-reactive protein levels decreased (P < .01) after the administration of effervescent glutamine formulation. Serum levels of interferon-gamma inducible protein-10, RANTES, and macrophage inflammatory protein-1ß were decreased after the treatment with effervescent glutamine formulation. No changes were observed in the serum levels of amino acids, hematological, toxicological, and biochemical parameters. In conclusion, the treatment during 30 days with effervescent glutamine formulation was well tolerated, promoted reduction of inflammation, and improved the beneficial effects of antiretroviral therapies in HIV/AIDS carrier patients.

Effect of curcumin supplementation on serum expression of select cytokines and chemokines in a female rat model of nonalcoholic steatohepatitis.

OBJECTIVE: We recently reported that curcumin supplementation in a metabolically (i.e., Western diet [WD]) and chemically (i.e., CCl4) induced female rat model of non-alcoholic steatohepatitis (NASH) was associated with lower liver pathology scores and molecular markers of inflammation. This occurred when curcumin was given during induction of disease (preventative arm; 8-week WD with or without curcumin [8WD + C vs. 8WD]) as well as when given after disease development (treatment arm; 12-week WD with or without curcumin during weeks 9-12 [12WD + C vs. 12WD]). Herein, we sought to extend our findings from that study by determining the effects of curcumin supplementation on cytokine/chemokine expression in serum collected from these same rats. RESULTS: 24 cytokines/chemokines were assayed. IL-2 (+ 80%) and IL-13 (+ 83%) were greater with curcumin supplementation in the prevention arm. IL-2 (+ 192%), IL-13 (+ 87%), IL-17A (+ 81%) and fractalkine (+ 121%) were higher while RANTES was lower (- 22%) with curcumin supplementation in the treatment arm (p < 0.05 for all). RANTES concentrations also correlated significantly with hepatic pathology scores of inflammation (r = 0.417, p = 0.008). Select serum cytokines/chemokines were affected with curcumin supplementation in this female rat model of NASH. Moreover, curcumin's effect(s) on RANTES and its association with liver disease pathogenesis and progression may warrant further investigation.

Effects of Desloratadine Citrate Disodium on Serum Immune Function Indices, Inflammatory Factors and Chemokines in Patients with Chronic Urticaria.

OBJECTIVE: To determine the effects of desloratadine citrate disodium on serum immunological function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) in patients with chronic urticaria. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Dermatology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi'an, China, from January 2017 to January 2018. METHODOLOGY: A total of 128 patients with chronic urticaria were randomly divided into a control group and an observation group, with 64 patients in each group. The patients in the control group were treated with loratadine and those in the observation group were treated with desloratadine citrate disodium. After 4 weeks of treatment, the serum levels of immune function indices (IgE, C3 and C4), inflammatory factors (IL-4, IL-17 and IL-33), and chemokines (MCP-1, RANTES and Eotaxin) were determined. RESULTS: After 4 weeks of treatment, the levels of serum IgE, IL-4, IL-17, IL-33, MCP-1, RANTES and Eotaxin in the observation group were lower than those in the control group (all p<0.001). The levels of serum C3 and C4 in the observation group were higher than those in the control group (both p<0.001). CONCLUSION: Desloratadine citrate disodium can effectively reduce the severity of chronic urticaria, and its therapeutic mechanism may be related to balancing Th1/Th2 cell function, regulating inflammatory mediators and inhibiting the action of chemokines.

Effects of Shaoyao-Gancao Decoction on Infarcted Cerebral Cortical Neurons: Suppression of the Inflammatory Response following Cerebral Ischemia-Reperfusion in a Rat Model.

The mechanisms by which Shaoyao-Gancao decoction (SGD) inhibits the production of inflammatory cytokines in serum and brain tissue after cerebral ischemia-reperfusion (CI-RP) in rats were investigated. A right middle cerebral artery occlusion was used to induce CI-RP after which the rats were divided into model (n = 39), SGD (n = 28), clopidogrel (n = 25) and sham operated (n = 34) groups. The Bederson scale was used to evaluate changes in behavioral indices. The levels of IL-1ß, TNF-α, MCP-1, IL-10, RANTES, VEGF, and TGF-ß1 in the serum and infarcted brain tissues were measured. Nissl body and immunohistochemical staining methods were used to detect biochemical changes in neurons, microglial cells, and astrocytes. Serum levels of VEGF, TNF-α, MCP-1, IL-1ß, and IL-10 increased significantly 24 h after CI-RP. In brain tissue, levels of TNF-α and IL-1ß significantly increased 24 h after CI-RP, whereas levels of TGF-ß1 and MCP-1 were significantly higher 96 h after CI-RP (P < 0.05). SGD or clopidogrel after CI-RP reduced TNF-α and IL-1ß levels in brain tissue and serum levels of MCP-1, IL-1ß, and IL-10. SGD increased the number of NeuN-positive cells in infarcted brain tissue and reduced the number of IBA1-positive and GFAP-positive cells. The efficacy of SGD was significantly higher than that of clopidogrel.

Effect of ZIP2 Gln/Arg/Leu (rs2234632) polymorphism on zinc homeostasis and inflammatory response following zinc supplementation.

Zinc dyshomeostasis may lead to an augmented production of proinflammatory cytokines promoting chronic inflammation and increasing the susceptibility to age-related diseases. Several studies suggest that the zinc transporter protein ZIP2 may play a relevant role in the immune system especially during zinc deficiency, while a polymorphism on the coding region of ZIP2 gene (Gln/Arg/Leu) has been associated with severe carotid artery disease. The aim of this study is to investigate the role of ZIP2 SNP on zinc and inflammatory status in 1090 elderly healthy free-living subjects enrolled in the ZincAge project and to assess the effect of zinc supplementation on zinc status, inflammatory mediators, and zinc transporter expression depending on ZIP2 genotype. ZIP2 Leu- (Arg43Arg) carriers showed enhanced IL-6, TNF-α, and RANTES plasma levels associated with decreased free cytosolic zinc in PBMCs and an upregulation of zinc transporters ZIP2, ZIP8, and Znt1. Moreover, Leu- subjects displayed significant decrement of inflammatory mediators such as MCP-1, TNF-α, and RANTES following zinc supplementation. In summary, this investigation provides new evidence on the effect of ZIP2 Gln/Arg/Leu polymorphism on proinflammatory mediators and zinc homeostasis in elderly population with a more pronounced anti-inflammatory effect of zinc supplementation in subjects carrying ZIP2 Leu- (Arg43Arg) genotype. These novel findings could be useful in identifying elderly subjects who may benefit of zinc intervention to decrease the inflammatory status and to prevent or delay the development of age-related diseases.

Protection of intestinal injury during heat stroke in mice by interleukin-6 pretreatment.

KEY POINTS: Heat stroke afflicts thousands of humans each year, worldwide. The immune system responds to hyperthermia exposure resulting in heat stroke by producing an array of immunological proteins, such as interleukin-6 (IL-6). However, the physiological functions of IL-6 and other cytokines in hyperthermia are poorly understood. We hypothesized that IL-6 plays a protective role in conditions of heat stroke. To test this, we gave small IL-6 supplements to mice prior to exposing them to hot environments sufficient to induce conditions of heat stroke. Pretreatment with IL-6 resulted in improved ability to withstand heat exposure in anaesthetized mice, it protected the intestine from injury, reducing the permeability of the intestinal barrier, and it attenuated the release of other cytokines involved in inflammation. The results support the hypothesis that IL-6 is a 'physiological stress hormone' that plays an important role in survival during acute life-threatening conditions such as heat stroke. ABSTRACT: The role of interleukin-6 (IL-6) in hyperthermia and heat stroke is poorly understood. Plasma IL-6 is elevated following hyperthermia in animals and humans, and IL-6 knockout mice are more intolerant of severe hyperthermia. We evaluated the effect of IL-6 supplementation on organ injury following severe hyperthermia exposure in anaesthetized mice. Two hours prior to hyperthermia, mice were treated with 0.6 µg intraperitoneal IL-6, or identical volumes of saline in controls. Mice were anaesthetized, gavaged with FITC-dextran for measures of gastrointestinal permeability, and exposed to incremental (0.5°C every 30 min) increases in temperature. Heating stopped when maximum core temperature (Tc) of 42.4°C was attained (Tc,max). The mice recovered at room temperature (≈22°C) for 30 or 120 min, at which time plasma and tissues were collected. IL-6-treated mice, on average, required ≈25 min longer to attain Tc,max . Injury and swelling of the villi in the duodenum was present in untreated mice after 30 min of recovery. These changes were blocked by IL-6 treatment. IL-6 also reduced gastrointestinal permeability, assayed by the accumulation of FITC-dextran in plasma. Plasma cytokines were also attenuated in IL-6-treated animals, including significant reductions in TNFα, MCP-1 (CXCL2), RANTES (CCL5) and KC (CCL5). The results demonstrate that IL-6 has a protective influence on the pattern of physiological responses to severe hyperthermia, suggesting that early endogenous expression of IL-6 may provide a protection from the development of organ damage and inflammation.

[Effects of artesunate on tumor necrosis factor alpha and chemotactic factors in the serum and the synoviocyte culture supernate of collagen-induced arthritis rats].

OBJECTIVE: To evaluate the effects of Artesunate on tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein (MCP-1), and on reduced activation normal T cell expressed and secreted (RANTES) in the serum and the synoviocyte culture supernate of collagen-induced arthritis (CIA) rats. METHODS: Eighty male Wistar rats were selected to establish the CIA rat model. On the 6th day after modeling, 60 rats with the sum of arthritis index of right metapedes and two propodium > or = 6 were selected, and randomly divided into 6 groups (n = 10), i.e., the blank control group, the CIA model control group (treated with normal saline, abbreviated as the CIA group), the MTX positive control group (abbreviated as the MTX group), the large dose Artesunate group (at the daily dose of 20 mg/kg), the moderate dose Artesunate group (at the daily dose of 10 mg/ kg), and the small dose of Artesunate group (at the daily dose of 2.5 mg/kg). Mice were sacrificed 7 days of immune injection and their venous blood was collected to obtain the serum. Meanwhile, the synovial tissues of the knee joint were taken by aseptic techniques and primary cultured for 48 h. The supernate was collected by centrifuge. The changes of MCP-1, RANTES, and TNF-alpha in the serum and the synoviocyte culture supernate were observed in each group before and after treatment using ELISA. RESULTS: Artesunate significantly decreased the expressions of TNF-alpha in the serum and the synoviocyte culture supernate, showing significant difference when compared with the model control groups (P < 0.05). There was no statistical difference in the large dose Artesunate group and the moderate dose Artesunate group when compared with the MTX group (P > 0.05). But statistical difference existed in the large dose Artesunate group, the moderate dose Artesunate group, and the MTX group when compared with the small dose Artesunate group (P < 0.05). Artesunate could significantly decrease the expressions of MCP-1 and RANTES in the serum and the synoviocyte culture supernate, showing statistical difference when compared with the model control group (P < 0.05). But no statistical difference existed when compared with the MTX group (P > 0.05). CONCLUSION: The mechanism of anti-inflammatory action and immune regulation of Artesunate might be correlated with the inhibition of inflammatory factor TNF-alpha and chemotactic factors MCP-1 and RANTES.

[Chemokine profile of Yusho patients].

Dioxins may have an impact on the human immunological system, which would increase the risk to develop allergic diseases, such as atopic dermatitis. In the present study, we measured serum levels of Th1- and Th2-favored chemokines in 233 Yusho patients who attended annual medical check-ups from 20.06 to 2009 and in 97 control subjects. Serum levels of CCL5, CCL17, and CCL27 in Yusho patients were significantly lower than those in control subjects. In addition, serum levels of some chemokines have weak correlations with blood levels of dioxins in either Yusho patients or control subjects.

Systemic inflammatory load in humans is suppressed by consumption of two formulations of dried, encapsulated juice concentrate.

Chronic inflammation contributes to an increased risk for developing chronic conditions such as cardiovascular disease, diabetes, and cancer. A high "inflammatory load" is defined as elevated inflammation markers in blood or other tissues. We evaluated several markers of systemic inflammation from healthy adults and tested the hypothesis that two formulations of encapsulated fruit and vegetable juice powder concentrate with added berry powders (FVB) or without (FV) could impact markers of inflammatory load. Using a double-blind, placebo-controlled approach, 117 subjects were randomly assigned to receive placebo, FV, or FVB capsules. Blood was drawn at baseline and after 60 d of capsule consumption. We measured inflammatory markers (high sensitivity C-Reactive Protein, Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein 1-ß, and Regulated upon Activation, Normal T cell Expressed and Secreted), superoxide dismutase, and micronutrients (ß-carotene, vitamin C, and vitamin E). Results showed Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein 1-ß, and RANTES levels were significantly reduced and superoxide dismutase and micronutrient levels were significantly increased in subjects consuming both FV and FVB, relative to placebo. Data suggest a potential health benefit by consuming either formulation of the encapsulated juice concentrates through their anti-inflammatory properties.

[Effects of three Chinese herbal antidotes (Herba artemisiae annuae, Herba hedyotis diffusae and Rhizoma cimicifugae) and their different combinations on regulated on activation normal T cell expressed and secreated expression in MRL/lpr mice].

OBJECTIVE: To explore the effects of three Chinese herbal antidotes, i.e. Herba Artemisiae annuae (A), Herba Hedyotis diffusae (H) and Rhizoma Cimicifugae (C), all were ingredients of Jiedu Quyu Ziyin Recipe, for adjusting the regulated on activation normal T cell expressed and secreated (RANTES), gene expression in serum and renal tissue of MRL/lpr mice. METHODS: Fifty-four MRL/lpr mice were randomized into 9 groups, with 6 in each, and intragastrically infused with A, H, C, A+H, H+C, A+C, A+H+C (all in dosage-form of decoction), prednisone suspension and physiological saline, respectively for 12 weeks. RANTES expression in serum and renal tissue of animals were detected with ELISA and RT-PCR at the end of the study. RESULTS: Levels of RANTES expression was significantly reduced in the prednisone treated group after treatment. Excepting no significant change being observed in the groups treated with A and C, the changes in the other groups were all milder than those in the group treated with A+H+C. CONCLUSION: Chinese herbal antidotes A, H and C in combination can significantly inhibit the RANTES expression in serum and renal tissue of MRL/lpr mice.

[Therapeutic effect of anti-anaphylaxis granule on chronic urticaria and its impact on serum levels of RANTES].

OBJECTIVE: To investigate the therapeutic effect of Anti-anaphylaxis Granule (AAG) on chronic urticaria and its impact on cytokine of regulated upon activation of normal T cells expressed and secreted (RANTES), eosinophil chemotactic factor (Eotaxin) and tumor necrosis factor-alpha (TNF-alpha). METHODS: The therapeutic effects of AAG and cetirizine on chronic urticaria patients allocated in two groups were observed respectively, and the serum levels of RANTES, Eotaxin and TNF-alpha in patients were measured by ELISA before and after treatment, and were compared with those in normal subjects. RESULTS: The therapeutic effects of AAG group were better in effective rate (88.5% vs 64.0%) and lower in the recurrent rate (5.6% vs 41.9%) than those cetirizine (all P<0.05). Serum levels of RANTES, Eotaxin and TNF-alpha in patients were higher than those in normal subjects (P<0.01), and they could be significantly reduced after AAG treatment (P<0.01). CONCLUSION: AAG has favorite effect for treatment of chronic urticaria, its regulation on serum levels of RANTES, Eotaxin and TNF-alpha may be the mechanism of action.

[Effect of Liuwei Dihuang soft capsule and Ginkgo leaf tablet on serum regulated upon activation, normal T cell expressed and secreted in patients with diabetes mellitus type 2].

OBJECTIVE: To investigate the effect of Liuwei Dihuang Soft Capsule(LDSC) and Ginkgo Leaf Tablet (GLT) on serum regulated upon activation, normal T cell expressed and secreted (RANTES) in the patients with diabetes mellitus type 2 (DM2). METHODS: Forty patients with early stage DM2 were randomly assigned to two groups, 20 in each group. Based on the conventional treatment with hypoglycemic agents, patients in the treated group were treated with LDSC plus GLT additionally, and those in the placebo group with placebo for 6 months, respectively. The levels of serum RANTES, blood glucose, blood lipids and glycosylated hemoglobin, as well as micro-content of albumin in urine were measured before and after treatment. RESULTS: In the treated group, the serum level of RANTES decreased significantly after treatment, and it was significantly lower as compared with that in the control group (P < 0.05). CONCLUSIONS: LDSC and GLT can decrease serum RANTES level in patients with DM2. They play a preventive and therapeutic role on diabetic complications by their anti-inflammatory effect.

Circulating chemoattractants RANTES, negatively related to endogenous androgens, and MCP-1 are differentially suppressed by hormone therapy and raloxifene.

BACKGROUND: The cardinal role of chronic inflammation in the development of atherosclerosis is increasingly being recognized. Estrogens may prevent the evolution of atherosclerosis by suppressing immune response. Furthermore, the conflicting reports on the cardiovascular effects of hormone therapy between observational and clinical trials have triggered interest on the effect of alternative therapies on the cardiovascular system. OBJECTIVE: The aim of this study was to assess the effect of estrogen, estrogen-progestin, tibolone and raloxifene therapy on circulating markers of chemotaxis in healthy postmenopausal women. METHODS: Eighty-eight postmenopausal women aged 44-62 years were randomly allocated to daily: (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and at 3 months. RESULTS: Endogenous testosterone and free androgen index (FAI) correlated negatively, while SHBG correlated positively with serum RANTES (testosterone: r=-0.27, p=0.033; FAI: r=-0.43, p=0.004: SHBG: r=0.34, p=0.026). Serum MCP-1 decreased significantly in the CEE group (baseline 125.3+/-51 pg/ml, 3 months 84.5+/-36.1 pg/ml, p=0.043), while no difference was detected between baseline and post-treatment levels in the other groups. Furthermore, a significant decrease in serum RANTES was observed at the end of 3 months only in the E2/NETA and the raloxifene group (E2/NETA baseline 8690.6+/-3880.0 pg/ml, 3 months 6894.0+/-1720.0 pg/ml, p=0.007; raloxifene baseline 9042.4+/-3765.6 pg/ml, 3 months 6718.1+/-2366.2 pg/ml, p=0.011). CONCLUSION: Endogenous androgens may suppress chemotactic response. Postmenopausal hormone therapy and raloxifene may inhibit the expression of chemoattractant molecules and thus attenuate inflammation. The relevance of these findings in terms of clinically established caridoprotection remains to be clarified.

Dietary fatty acid unsaturation levels, lipoprotein oxidation and circulating chemokine in experimentally induced atherosclerotic rats.

The dietary balance of long-chain fatty acids may influence processes involving leukocyte endothelial interactions, such as atherogenesis and inflammation. The relationship between proatherogenic lipoproteins and chemotactic motility is still controversial. However, the interaction of the former can increase recruitment of monocytes to the vessel walls and accelerate the events of atherogenesis. The current study examined the effects of unsaturated fatty acid levels on the oxidative susceptibility of lipoprotein, chemokine expressions and their relationship to atherosclerotic lesion development in experimental rats. Male Wistar rats were fed an atherogenic diet for 4 months and the diet was then supplemented with 10% v/w of virgin olive oil (OO group), sunflower oil (SO group) or fish oil (FO group) for 4 and 8 weeks. Blood samples were collected at four time points: at baseline, after feeding with the atherogenic diet and during the dietary regimen (4 and 8 weeks). Plasma lipid profile and lipoprotein oxidative susceptibility (LOS), C-reactive protein (CRP), monocyte chemoattractant protein (MCP-1), and regulated upon activation normal T-cell expressed and secreted (RANTES) were measured. The superoxide dismutase (SOD) and reduced glutathione (GSH) antioxidant activities were also studied in aortic segments. Histological assessment of the aortic segment was determined. Compared to baseline data, the high-fat and cholesterol-enriched diet increased atheroma formation, plasma LOS and inflammatory indexes (CRP, MCP-1, RANTES). However, it dramatically reduced aortic SOD and GSH contents. Dietary treatment of atherosclerotic rats with OO greatly reduced LOS and remarkably increased aortic SOD and GSH contents as compared to the SO- and FO-treated groups. The FO-supplemented diet had a more pronounced lowering effect on MCP-1 and RANTES compared to the OO and SO diets. In conclusion, this study demonstrated a strong relationship between LOS and circulating levels of chemokines. OO is a potent antioxidant and moderate anti-inflammatory, which effectively reduced aortic atherosclerotic lesions more than the SO- or FO-treated groups in male Wistar rats.

Long-term treatment with nifedipine modulates procoagulant marker and C-C chemokine in hypertensive patients with type 2 diabetes mellitus.

In type 2 diabetes mellitus, there is increased risk of nephropathy and cardiovascular complications and the incidence of renal failure increases in advanced stages of the disease. Nifedipine, a dihydropyridine-type calcium antagonist, improves endothelial function in hypercholesterolemia by enhancing nitric oxide function, and increases endothelial nitric oxide bioavailability by antioxidative mechanisms. We administered nifedipine, 50 mg/day, to the hypertensive patients for 12 months. There were no other changes in any of the patient's pharmacologic regimen during nifedipine treatment. Clinical and biochemical data obtained before and after nifedipine administration were compared. All markers were measured by ELISA. The levels of platelet activation markers (CD62P, CD63, PAC-1, and Annexin V), microparticles (PDMP and MDMP), RANTES and soluble adhesion markers (sP-selectin and sVCAM-1) differed in the control group and the hypertension group. The levels of these markers were also different in hypertensive patients with and without type 2 diabetes but were unchanged in patients without diabetes in comparison to the control group. However, the concentrations of MDMPs, chemokines, and soluble adhesion markers in hypertensive patients without type 2 diabetes decreased significantly following nifedipine treatment, although the level of RANTES was unchanged. Systolic blood pressure correlated with CD62P, CD63, annexin V, and RANTES levels, and diastolic blood pressure with CD62P and annexin V levels. The effect of nifedipine on platelet activation markers and C-C chemokines in the present study indicates potential effectiveness of calcium antagonist therapy for hypertensive patients with type 2 diabetes.

Storage of platelets in additive solutions: the effects of magnesium and potassium on the release of RANTES, beta-thromboglobulin, platelet factor 4 and interleukin-7, during storage.

BACKGROUND AND OBJECTIVES: Several studies have suggested that the accumulation of cytokines during storage of platelet concentrates may mediate non-haemolytic transfusion reactions. Prestorage leucodepletion can prevent the release of cytokines from white blood cells during storage, but not the release of platelet-derived cytokines. Therefore, we investigated whether the addition of magnesium and potassium to platelets stored in a platelet additive solution (PAS) would affect the generation of cytokines during platelet storage. MATERIALS AND METHODS: Platelets were prepared from buffy coats using different suspension media: plasma; 70% PAS-III + 30% plasma; 70% PAS-III supplemented with magnesium and potassium +30% plasma; and 80% PAS-III supplemented with magnesium and potassium +20% plasma. The levels of certain cytokines--regulated on activation, normal, T-cell expressed, and secreted (RANTES), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4) and interleukin-7 (IL-7)--were measured by enzyme-linked immunosorbent assay (ELISA) on days 1, 5 and 7. RESULTS: The concentrations of RANTES, beta-TG, PF4 and IL-7 increased, during storage, in all units. The increase was significantly greater in units stored in 70% PAS-III +30% plasma than in the other three suspension media. The storage of platelets in 70% PAS-III supplemented with magnesium and potassium +30% plasma significantly reduced the concentrations of platelet derived-cytokines during storage, as compared to platelets stored in 70% PAS-III + 30% plasma alone. CONCLUSIONS: The concentrations of platelet-derived cytokines increased, to a significantly greater extent, when platelets were stored in PAS-III than in plasma. However, when magnesium and potassium were added to PAS-III, the concentrations of platelet-derived cytokines obtained during storage were about the same as those produced by platelets stored in plasma.

Folic acid treatment reduces chemokine release from peripheral blood mononuclear cells in hyperhomocysteinemic subjects.

Elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease. However, the mechanisms by which hyperhomocysteinemia induces vascular disease are uncertain. An early step in atherogenesis involves leukocyte migration into the arterial wall, a process regulated in part by chemokines. We hypothesized that homocysteine may exert its atherogenic effect in part through chemokine-mediated mechanisms, and in the present study, we examined the effects of folic acid supplementation for 6 weeks on chemokine levels in hyperhomocysteinemic individuals. Data showed the following: (1) Compared with control subjects, hyperhomocysteinemic subjects had elevated plasma levels of the CXC chemokines, epithelial neutrophil-activating peptide (ENA)-78 (P<0.05), and growth-regulated oncogene (GRO)alpha (P=0.088), and homocysteine was significantly correlated with ENA-78 and GROalpha. (2) During folic acid treatment, normalization of homocysteine levels was accompanied by a marked reduction in oxidized low density lipoprotein-stimulated release of CXC chemokines (ie, GROalpha, ENA-78, and interleukin-8) and CC chemokines (ie, monocyte chemoattractant peptide-1 and RANTES) in peripheral blood mononuclear cells from these individuals. (3) The oxidized low density lipoprotein-induced release of ENA-78 from peripheral blood mononuclear cells from control subjects was significantly reduced when cells were incubated in the presence of folic acid. These data may suggest that homocysteine exerts atherogenic effects in part by enhancing chemokine responses in cells involved in atherogenesis and that folic acid supplementation may downregulate these inflammatory responses.

The synthesis of Rantes, G-CSF, IL-4, IL-5, IL-6, IL-12 and IL-13 in human whole-blood cultures is modulated by an extract from Eleutherococcus senticosus L. roots.

An ethanol extract derived from the roots of Eleutherococcus senticosus was found to influence markedly the cytokine synthesis of activated whole blood cultures of ten healthy volunteers. Whereas the synthesis of Rantes was increased over a wide range of concentrations, the release of IL-4, IL-5 and IL-12 was significantly inhibited. An inhibition at higher concentrations, switching to a stimulation at lower doses of the extract was seen with G-CSF, IL-6 and IL-13. From these particular immuno-pharmacological effects of Eleutherococcus senticosus we suggest this herbal preparation possesses immuno-modulatory potency, rather than just being immuno-suppressive or -stimulating.

Chemokines, nitric oxide and antiarthritic effects of 9-(2-phosphonomethoxyethyl)adenine (Adefovir).

Antiarthritic effects of two acyclic nucleoside phosphonates, 9-(2-phosphonomethoxyethyl)adenine (PMEA; Adefovir) and 9-(2-phosphonomethoxypropyl)adenine (PMPA), as well as their more bioavailable prodrugs, bis(pivaloyloxymethyl)ester of PMEA [bis(POM)-PMEA; Adefovir Dipivoxil] and bis(isopropyloxycarbonyloxymethyl)ester of PMPA [bis(POC)-PMPA], were investigated in a model of adjuvant-induced arthritis in Lewis rats. The drugs were injected subcutaneously at doses of 5-50 mg/kg. PMEA and its prodrug inhibited by > 80% arthritic paw swelling, splenomegaly and fibroadhesive perisplenitis. Both prophylactic and therapeutic dosing regimens were effective. Neither PMPA nor bis(POC)-PMPA suppressed development of arthritic lesions. Substantially reduced nitrite + nitrate levels were detected in serum and urine of PMEA-treated animals as compared to those of untreated diseased controls. Also, complete suppression of the disease-associated, greatly enhanced systemic levels of the chemokine, RANTES (regulated upon activation, normal T cell expressed and secreted), was observed in rats injected with PMEA. Additional in vitro studies showed that PMEA does not change, PMPA enhances, and both prodrugs inhibit the immune-activated NO production. Under the same conditions PMEA inhibits, while PMPA slightly stimulates, secretion of RANTES. Collectively, these data suggest that the in vivo-inhibited production of nitric oxide (NO) is a consequence rather than a mechanism of antiarthritic action of PMEA. Possible mechanisms for the anti-RANTES activity of PMEA remains to be firmly established.