Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped into several protein families that are referred to as tumor necrosis factors, interleukins, interferons, and colony-stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis, and metastasis, all phenomena in which cytokines are prominent players. The data here suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancerrelated disorders.

Chemokines are small proteins that primarily regulate the traffic of leukocytes under homeostatic conditions and during specific immune responses. The chemokine-chemokine receptor system comprises almost 50 chemokines and approximately 20 chemokine receptors; thus, there is no unique ligand for each receptor and the binding of different chemokines to the same receptor might have disparate effects. Complicating the system further, these effects depend on the cellular milieu. In cancer, although chemokines are associated primarily with the generation of a protumoral microenvironment and organ-directed metastasis, they also mediate other phenomena related to disease progression, such as angiogenesis and even chemoresistance. Therefore, the chemokine system is becoming a target in cancer therapeutics. We review the emerging data and correlations between chemokines/chemokine receptors and breast cancer, their implications in cancer progression, and possible therapeutic strategies that exploit the chemokine system.

In breast cancer, an uncontrolled cell proliferation leads to tumor formation and development of a multifactorial disease. Metastasis is a complex process that involves tumor spread to distant parts of the body from its original site. Metastatic dissemination represents the main physiopathology of cancer. Inter-and intracellular communication in all systems in vertebrates is mediated by cytokines, which are highly inducible, secretory proteins, produced not only by immune system cells, but also by endocrine and nervous system cells. It has become clear in recent years that cytokines, as well as their receptors are produced in the organisms under physiological and pathological conditions; recently, they have been closely related to breast cancer metastasis. The exact initiation process of breast cancer metastasis is unknown, although several hypotheses have emerged. In this study, we thoroughly reviewed the role of several cytokines in breast cancer metastasis. Data reviewed suggest that cytokines and growth factors are key players in the breast cancer metastasis induction. This knowledge must be considered with the aim to development of new therapeutic approaches to counter breast cancer metastasis.

Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.

Aims The zoonotic nematode Toxocara canis causes larva migrans syndrome that induces an immune response characterized by the production of antibodies and eosinophilia. A Th2 polarization has been associated with the infection, but there are still details of the cellular and humoral immune response that need to be described. Thus, the aim of this study was to describe the systemic host immune response to T canis chronic infection in a mouse model. Methods and Results BALB/c mice were inoculated once with 500 T canis embryonated eggs, per os. After 49 days, the amounts of larval found in brain and muscle tissues were statistically two and four times higher, respectively, than the amounts found in lung, liver, kidney or heart tissues. Splenic proportions of F4/80+ cells, as well as B, cytotoxic T and CD4+Foxp3+ lymphocytes, were statistically higher (P ≤ .05, P ≤ .01, P ≤ .001 and P ≤ .001, respectively) as compared with control mice. In lymph nodes, some of these proportions changed, with the exception of F4/80+ cells. IgG1 levels in infected mice sera were increased. IL‐4, IL‐10 and VEGF levels were statistically higher in spleen (P ≤ .05, all) and sera (P ≤ .01, P ≤ .05 and P ≤ .05, respectively) in the infected mice. Also, in infected animals, IL‐5 serum levels were increased (P ≤ .01). Conclusion These results suggest that T canis chronic infection in BALB/c mice results in a type 2 response with an incipient regulatory response.

It has been widely reported that the incidence and the severity of natural parasitic infections are different between males and females of several species, including humans. This sexual dimorphism involves a distinct exposure of males and females to various parasite infective stages, differential effects of sex steroids on immune cells, and direct effects of these steroids on parasites, among others. Typically, for a large number of parasitic diseases, the prevalence and intensity is higher in males than females; however, in several parasitic infections, males are more resistant than females. In the present work, we review the effects of sex hormones on immunity to protozoa and helminth parasites, which are the causal agents of several diseases in humans, and discuss the most recent research related to the role of sex steroids in the complex host-parasite relationship.

Background: As a result of human socioeconomic activity, industrial wastes have increased distressingly. Plastic pollution is globally distributed across the world due to its properties of buoyancy and durability. A big health hazard is the sorption of toxicants to plastic while traveling through the environment. Two broad classes of plastic-related chemicals are of critical concern for human health-bisphenols and phthalates. Bisphenol A (BPA) is an endocrine-disruptor compound (EDC) with estrogenic activity. It is used in the production of materials that are used daily. The endocrine modulating activity of BPA and its effects on reproductive health has been widely studied. BPA also has effects on the immune system; however, they are poorly investigated and the available data are inconclusive. Phthalates are also EDCs used as plasticizers in a wide array of daily-use products. Since these compounds are not covalently bound to the plastic matrix, they easily leach out from it, leading to high human exposure. These compounds exert several cell effects through modulating different endocrine pathways, such as estrogen, androgen, peroxisome proliferator-activated receptor gamma, and arylhydrocarbon receptor pathways. The exposure to both classes of plastic derivatives during critical periods has detrimental effects on human health. Methods: In this review, we have compiled the most important of their perinatal effects on the function of the immune system and their relationship to the development of different types of cancer. Results/Conclusion: The administration of bisphenols and phthalates during critical stages of development affects important immune system components, and the immune function; which might be related to the development of different diseases including cancer.

Susceptibility to malaria differs between females and males, and this sexual dimorphism may have important implications for the effects of vaccines and drugs. However, little is known about the mechanisms mediating these sexual differences. Because the main differences between sexes are dictated by sex hormones, we studied the effect of gonadal steroids on immune responses to malaria in CBA/Ca mice. We decreased sex hormones levels by gonadectomy and evaluated the splenic index and the cells involved in the immune response, including T cells (CD3(+), CD4(+), CD8(+) and NK(+)), B cells and macrophages (Mac-3(+)) in the spleens of female and male mice infected with Plasmodium berghei ANKA. In addition, we measured antibody and cytokine levels in blood. Gonadectomy increased T(+) and B(+) splenic cells in both sexes but increased Mac-3(+) cells only in male mice. By contrast, gonadectomy decreased the NK(+) cell population only in male mice. In general, female mice developed higher antibody levels than males. Contrary to our expectations, gonadectomy increased the synthesis of IgG1, IgG2b, IgG3, and total IgG in female mice, indicating negative regulation of antibody production by female sex hormones. Gonadectomy increased the synthesis of tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) only in female mice, suggesting that female sex hormones have anti-inflammatory properties. This work demonstrates that the levels of sex hormones affect the immune response and should be considered when designing malaria vaccines.