Background—Adaptive T-cell response is promoted during atherogenesis and results in the differentiation of naïve CD4+T cells to effector and/or memory cells of specialized T-cell subsets. Aim of this work was to investigate the relationship between circulating CD4+T-cell subsets and atherosclerosis.Methods and Results—We analyzed 57 subsets of circulating CD4+T cells by 10-parameter/8-color polychromatic flow cytometry (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA-DR) in peripheral blood from 313 subjects derived from 2 independent cohorts. In the first cohort of subjects from a free-living population (n=183), effector memory T cells (TEM: CD3+CD4+CD45RA−CD45RO+CCR7− cells) were strongly related with intima-media thickness of the common carotid artery, even after adjustment for age (r=0.27; P<0.001). Of note, a significant correlation between TEM and low-density lipoproteins was observed. In the second cohort (n=130), TEM levels were significantly increased in patients with chronic stable angina or acute myocardial infarction compared with controls. HLA-DR+TEM were the TEM subpopulation with the strongest association with the atherosclerotic process (r=0.37; P<0.01). Finally, in animal models of atherosclerosis, TEM (identified as CD4+CD44+CD62L−) were significantly increased in low-density lipoprotein receptor and apolipoprotein E deficient mice compared with controls and were correlated with the extent of atherosclerotic lesions in the aortic root (r=0.56; P<0.01).Conclusions—Circulating TEM cells are associated with increased atherosclerosis and coronary artery disease in humans and in animal models and could represent a key CD4+T-cell subset related to the atherosclerotic process. (J Am Heart Assoc. 2012;1:27-41.)

Objective-Regulatory T (Treg) cells play a protective role in experimental atherosclerosis. In the present study, we investigated whether the levels of circulating Treg cells relate to the degree of atherosclerosis in carotid and coronary arteries. Methods and Results-We studied 2 distinct populations: (1) 113 subjects, selected from a free-living population (carotid study), in which we measured the intima-media thickness of the common carotid artery, as a surrogate marker of initial atherosclerosis; and (2) 75 controls and 125 patients with coronary artery disease (coronary study): 36 with chronic stable angina, 50 with non-ST-elevation acute coronary syndrome, 39 with ST-elevation acute myocardial infarction. Treg-cell levels were evaluated by flow cytometry (Treg cells identified as CD3 ϩ CD4 ϩ CD25 high CD127 low ) and by mRNA expression of forkhead box P3 or of Treg-associated cytokine interleukin 10. In the carotid study, no correlation was observed between Treg-cell levels and intima-media thickness. No differences in Treg-cell levels were observed comparing rapid versus slow intima-media thickness progressors from a subgroup of patients (nϭ65), in which prospective data on 6-year intima-media thickness progression were available. In the coronary group, Treg-cell levels were not altered in chronic stable angina patients. In contrast, nonunivocal variations were observed in patients suffering an acute coronary syndrome (with a Treg-cell increase in ST-elevation acute myocardial infarction and a Treg-cell decrease in non-ST-elevation acute coronary syndrome patients). Key Words: regulatory T cells Ⅲ coronary artery disease Ⅲ flow cytometry Ⅲ carotid artery intima-media thickness Ⅲ acute coronary syndrome T cells play a role in atherosclerosis and in acute manifestation of plaque destabilization. 1 The activation of inflammatory pathways in atherosclerosis and in coronary artery disease (CAD) is not confined to coronary lesions but involves the activation of neutrophils, monocytes, and lymphocytes (ie, CD69 Conclusion-Theϩ , HLA-DR ϩ , and CD 137 ϩ T cells) in peripheral blood in particular during acute coronary syndromes (ACSs). [2][3][4] On the other hand, regulatory T (Treg) cells reduce the development of experimental atherosclerosis acting both systemically and within the lesion. 5,6 Immunostaining of human atherosclerotic plaques showed that Treg cells are present during all stages of plaque development in the intima and adventitia. 7 In general, Treg cells play a key role in the maintenance of immunologic self-tolerance and negative control of a variety of pathological immune responses. 8 Several subsets of Treg cells with distinct phenotypes and distinct mechanisms of action have been described (see Sakaguchi et al,8 Roncarolo et al, 9 and O'Garra and Vieira 10 for review). Treg cells mediate the immunoregulatory function by producing cytokines, such as interleukin (IL)-10 and See accompanying article on page 1679 ϩ Treg cells, which have increased ability of homing and trafficking to inflamed nonly...

Objective. To assess local expression and plasma levels of pentraxin 3 (PTX3) in patients with giant cell arteritis (GCA).Methods. Plasma and serum samples were obtained from 75 patients with GCA (20 of whom had experienced optic nerve ischemia in the previous 3 weeks and 24 of whom had experienced symptom onset in the previous 6 months and had no history of optic nerve ischemia) and 63 controls (35 age-matched healthy subjects, 15 patients with rheumatoid arthritis, and 13 patients with chronic stable angina). In 9 patients in whom GCA was recently diagnosed, circulating levels of interleukin-1␤ (IL-1␤), IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p70, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1␣ (MIP-1␣), CCL4/MIP-1␤, CCL11/eotaxin, CXCL9/ monokine induced by interferon-␥, CXCL10/interferon-␥-inducible 10-kd protein, tumor necrosis factor ␣ (TNF␣), interferon-␥, vascular endothelial growth factor (VEGF), granulocyte-macrophage colonystimulating factor, and FasL were measured via a multiplexed cytometric assay. PTX3 and VEGF concentrations were assessed by enzyme-linked immunosorbent assay. PTX3 and CD68 expression were determined by immunohistochemistry and immunofluorescence on temporal artery samples.Results. GCA patients with very recent optic nerve ischemia had significantly higher PTX3 and VEGF levels compared to other GCA patients and controls. GCA patients with a disease duration of <6 months had significantly higher PTX3 levels compared to other GCA patients and controls. Immunohistochemistry revealed selective PTX3 expression in the wall of inflamed arteries.Conclusion. Our findings indicate that local expression of PTX3 is a feature of vascular inflammation in GCA; elevated circulating levels of PTX3 identify patients with very recent optic nerve ischemia or a recent diagnosis. Optic nerve ischemia is also associated with increased circulating VEGF levels.

Rationale: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6 + ) levels or very low-IL-6 – levels. Objective: We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response. Methods and Results: We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6 + STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6 − STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6 + STEMI and IL-6 − STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6 + STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and monokine induced by interferon-γ. IL-10 was increased both in IL-6 + STEMI and IL-6 − STEMI patients compared with controls. IL-6 + IL-10 + STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6 − IL-10 + STEMI patients. We combined IL-10 and monokine induced by interferon-γ (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death. Conclusions: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and immune-modulating therapies.

Ginger has a pain-reducing effect and it can modulate pain through various mechanisms: inhibition of prostaglandins via the COX and LOX-pathways, antioxidant activity, inibition of the transcription factor nf-kB, or acting as agonist of vanilloid nociceptor. This narrative review summarizes the last 10-year of randomized controlled trials (RCTs), in which ginger was traditionally used as a pain reliever for dysmenorrhea, delayed onset muscle soreness (DOMS), osteoarthritis (AO), chronic low back pain (CLBP), and migraine. Regarding dysmenorrhea, six eligible studies suggest a promising effect of oral ginger. As concerned with DOMS, the four eligible RCTs suggested a reduction of inflammation after oral and topical ginger administration. Regarding knee AO, nine RCTs agree in stating that oral and topical use of ginger seems to be effective against pain, while other did not find significant differences. One RCT considered the use of ginger in migraine and suggested its beneficial activity. Finally, one RCT evaluated the effects of Swedish massage with aromatic ginger oil on CLBP demonstrated a reduction in pain. The use of ginger for its pain lowering effect is safe and promising, even though more studies are needed to create a consensus about the dosage of ginger useful for long-term therapy. K E Y W O R D S chronic low back pain, dysmenorrhea, ginger, knee osteoarthritis, myalgia, pain 1 | INTRODUCTION Zingiber officinale Roscoe (Zingiberaceae family), commonly known as ginger is a climbing perennial plant, indigenous to southeastern Asia. Ginger extract is a mixture of many biologically active constituents (Grzanna, Lindmark, & Frondoza, 2005). These compounds are numerous and vary depending on the place of origin and whether the rhizomes are fresh or dry (Ali, Blunden, Tanira, & Nemmar, 2008). More than 400 chemical substances have been isolated and identified in ginger rhizomes extracts, and new ones are still being discov