Atherosclerosis is considered a chronic inflammatory disease in which monocytes and macrophages are critical. These cells express CD14, toll-like receptor (TLR) 2, and TLR4 on their surfaces, are activated by minimally modified low-density lipoprotein (mmLDL) and are capable of secreting pro-inflammatory cytokines. The aim of this research was thus to demonstrate that the activation of CD14, TLR2, and TLR4 by mmLDL induces the secretion of cytokines. Methods Human monocytes and macrophages were incubated with monoclonal antibodies specific for CD14, TLR4, and TLR2 prior to stimulation with mmLDL. Cytokine secretion was then compared to that observed upon mmLDL stimulation in untreated cells. Results Stimulation with mmLDL induced the secretion of pro-inflammatory cytokines. Blocking CD14 in monocytes inhibited secretion of interleukin (IL)-1β (72%), IL-6 (58%) and IL-10 (63%), and blocking TLR4 inhibited secretion of IL-1β by 67%, IL-6 by 63% and IL-10 by 60%. Blocking both receptors inhibited secretion of IL-1β by 73%, IL-6 by 69% and IL-10 by 63%. Furthermore, blocking TLR2 inhibited secretion of IL-1β by 65%, IL-6 by 62% and IL-10 by 75%. In macrophages, we found similar results: blocking CD14 inhibited secretion of IL-1β by 59%, IL-6 by 52% and IL-10 by 65%; blocking TLR4 inhibited secretion of IL-1β by 53%, IL-6 by 63% and IL-10 by 61%; and blocking both receptors inhibited secretion of IL-1β by 69%, IL-6 by 67% and IL-10 by 65%. Blocking TLR2 in macrophages inhibited secretion of IL-1β by 57%, IL-6 by 40% and IL-10 by 72%. Conclusion Our study demonstrates that CD14, TLR4, and TLR2 participate in the immune response against mmLDL by inducing the production of pro-inflammatory cytokines in both monocytes and macrophages. These findings suggest that the activation of these receptors by mmLDL contributes to the inflammatory process of atherosclerosis.

Background: Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus.Results: Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor.Conclusions: We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.

Macrophages in atherosclerosis and myocardial infarction have diverse functions, such as foam cell formation and the induction of an inflammatory response that promotes ventricular dysfunction in the heart. Exosomes are small vesicles released by many different types of cells, such as macrophages, dendritic cells, platelets and other immunoregulatory cells, that facilitate communication with other cells, modulating the biological functions of recipient cells. Exosomes offer a novel therapeutic approach for the polarization of macrophages involved in cardiovascular diseases. In this review, we provide an overview of the biological role of macrophages in atherosclerosis and myocardial infarction and the effects of exosomes on these cells as therapeutic agents in the disease.

Background: Most infections with human papillomavirus (HPV) are resolved without clinical intervention, but a minority evolves into chronic lesions of distinct grades, including cervical-uterine cancer. It is known that in most cases the immune system mediates elimination of HPV infection. However, the mechanism of immune evasion leading to HPV persistence and development of early cervical lesions is not fully understood. The aim of the present work was to evaluate the potential of peripheral blood leukocytes (PBL) from low-grade squamous intraepithelial lesions (LSIL) patients to be activated ex-vivo by vaccine antigens, the participation of cytotoxic lymphocytes and regulatory T cells, and to determine the secretion of Th1 and Th2 cytokines mediated by stimulation of T cell receptors. Results: We found that PBL from LSIL patients showed a significantly lower proliferation rate to vaccine antigens as compared to that of healthy donors, even though there was not a difference in the presence of antibodies to those antigens in sera from both groups. We did not find differences in either the frequency of CD4 + CD25 + FoxP3+ in PBL, or the levels of IL-4, IL-5 and IL-10 in plasma or conditioned media from PBL incubated with TcR agonists in vitro, between the two groups. However, we detected a lower production of IL-2 and a higher proportion of CD8 + IFNγ + cells in PBL from LSIL patients as compared with PBL from normal donors. We also observed that PBL from patients infected by HPV-16 and −18 were not able to proliferate in the presence of soluble HPV antigens added to the culture; however, a high level of proliferation was attained when these antigens were presented by activated dendritic cells. Conclusions: Our results suggest that the immunodeficiency reported in LSIL patients could be due to the inability of specific cytotoxic T lymphocytes that for some unknown reason are present but unable to mount a response when challenged with their antigens, probably related to an in situ IL-2 production deficiency.

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by persistent inflammation. Reliable biomarkers for predicting disease reactivation are lacking. This study aimed to investigate serum cytokines and cytotoxic molecules in both the inactive (iSLE) and active (aSLE) phases to identify potential predictors of disease activity. Methods: Fifty-five SLE patients were classified as having iSLE (n = 36) or aSLE (n = 19) on the basis of clinical parameters and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Serum levels of cytokines, cytotoxic molecules, and CD8⁺ cells were analyzed through flow cytometry and principal component analysis (PCA). Additionally, seventeen healthy donors (HDs) served as a control group. Results: Serum perforin (median: 2219 pg/mL; p = 0.0020) and granulysin (median: 1347 pg/mL; p = 0.010) levels were significantly higher in patients with aSLE than in patients with iSLE. In contrast, sFas levels were elevated in both SLE groups compared with those in the HD group. Moreover, increased perforin and granulysin levels were correlated with increased SLEDAI-2K scores, and the proportion of cytotoxic cells (CD8⁺granzyme-B⁺perforin⁺ cells) was correlated with disease activity. Conclusions: The increased levels of cytotoxic molecules and the high CD8⁺ cell proportions suggest that integrating these parameters with traditional biomarkers could enhance disease monitoring and management.

Pro-inflammatory molecules and low-density lipoproteins play essential roles in the atherosclerosis. The aim of our study was to establish an association among the cytokines secreted by peripheral blood mononuclear cells and the serum concentration in patients with unstable angina and coronary outward remodeling before and after percutaneous coronary intervention. The clinical and coronary responses were evaluated 6 months after the procedure. Twenty-two patients with unstable angina were evaluated prior to after percutaneous coronary intervention and 6 months after procedure by coronary intravascular ultrasound. Eleven of the patients had recurrent angina, while 9 presented restenosis and an increase in the percentage of total plaque area. These 11 patients displayed higher levels of C-reactive protein than those without coronary events (1.27 vs. 0.43 mg/dl, respectively; p = 0.029) and a tendency to increase levels of interleukin (IL)-8 and transforming growth factor-β1, but lower levels of IL-10 (52.09 vs. 141.5 pg/ml, respectively; p = 0.035). Activated peripheral blood mononuclear cells from patients with restenosis presented higher levels of proliferation, CD86 expression and higher IL-1, and increased IL-10 compared to those in patients without restenosis. Patients with unstable angina and coronary outward remodeling who displayed a pro-inflammatory response experienced recurrent coronary events and an increased percentage of total plaque area. In contrast, better outcomes were observed in patients with anti-inflammatory responses. This response could be secondary to low-density lipoproteins.