Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy

Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) neurons cell body (neuronopathy/ganglionopathy). In addition, antineoplastic treatments may affect the blood brain barrier integrity, leading to cognitive impairment that may be severe and long-lasting. CIPN may affect patient quality of life leading to modification or discontinuation of the anticancer therapy. Although the mechanisms of the damage are not completely understood, several hypotheses have been proposed, among which neuroinflammation is now emerging to be relevant in CIPN pathophysiology. In this review, we consider different aspects of neuro-immune interactions in several CIPN preclinical studies which suggest a critical connection between chemotherapeutic agents and neurotoxicity. The features of the neuroinflammatory processes may be different depending on the type of drug (platinum derivatives, taxanes, vinca alkaloids and proteasome inhibitors). In particular, recent studies have demonstrated an involvement of the immune response (both innate and adaptive) and the stimulation and secretion of mediators (cytokines and chemokines) that may be responsible for the painful symptoms, whereas glial cells such as satellite and Schwann cells might contribute to the maintenance of the neuroinflammatory process in DRG and axons respectively. Moreover, neuroinflammatory components have also been shown in the spinal cord with microglia and astrocytes playing an important role in CIPN development. Taking together, better understanding of these aspects would permit the development of possible strategies in order to improve the management of CIPN.

Extracellular vesicles in the host-helminth communication: biomedical applications

Extracellular vesicles participate in intercellular communications, altogether with classic mechanisms like direct contact between cells and the secretion of mediators. They have attracted considerable interest since their discovery in reticulocytes in 1983. The term includes different types of vesicles that vary in size and origin, with exosomes, microvesicles and apoptotic bodies as the major ones. These structures are sorrounded by a lipid membrane, where various types of receptors are located, and can carry different cargo molecules, including sugars, proteins, nucleic acids and metabolites. They have been described in all kingdoms in nature (participating in both intercellular and inter-specific communications), in all types of biological fluids (as part of liquid biopsy). In fact, their presence in samples from both physiological and pathological processes has suggested them as excellent biomarkers. Their role in health and disease is being widely investigated. In this context, the study of extracellular vesicles produced by parasites, and specifically by helminths, constitutes a growing field of research, with great biomedical interest, mainly in the control of infections caused by them. In fact, these vesicles can be used to generate rapid and specific diagnosis systems, to produce new tools for vaccination, and to identify targets for new treatments. The ability of extracellular vesicles to modulate the immune response also opens new possibilities for their use against autoimmune diseases.

Extract from Bougainvillea xbuttiana (Variety Orange) Inhibits Production of LPS-Induced Inflammatory Mediators in Macrophages and Exerts a Protective Effect In Vivo

Background. Different pharmacological properties, such as antioxidant, antiproliferative, and anti-inflammatory properties, have been described among natural products. We previously described that the Bougainvillea xbuttiana (Variety Orange) ethanolic extract (BxbO) has an anti-inflammatory effect; however, this action is not fully understood. In this study, the action of the BxbO extract on the secretion of inflammatory mediators in two experimental models, in vitro and in vivo, after LPS challenge was evaluated. Methods. Peritoneal macrophages were obtained from female BALB/c mice and LPS-challenged with or without the BxbO extract. For the evaluation of mediators, the supernatants at 0, 12, 24, 36, and 48 hours were collected. For in vivo estimation, groups of female BALB/c mice were first intraperitoneously injected with different amounts of LPS and later administered the oral BxbO extract (v.o.) for 144 hours. To understand the mechanism of action, sera obtained from mice were collected at 0, 2, 4, 8, 12, and 24 hours after LPS challenge (with or without BxbO) for the detection of mediators. Results. The results showed that, in both peritoneal macrophages and sera of mice treated with the BxbO extract 1 hour before or together with LPS challenge, proinflammatory cytokines and nitric oxide release were unquestionably repressed. In contrast, in both systems studied here, the IL-10 levels were elevated to 5 to 9 times. At lethal doses of LPS, the BxbO extract treatment was found to protect animals from death. Conclusions. The results revealed that the inhibitory, protective, and benign effects of the BxbO extract were due to its capacity to balance the secretion of mediators.

Exosomes and communication between tumours and the immune system: are all exosomes equal?

Communication between cells is particularly important during tumour progression. Communication can take place through direct cell–cell interactions, but also through extracellular secretion of mediators acting at a distance. These mediators can be either soluble molecules or more complex structures called membrane vesicles, enclosing soluble factors within a lipid bilayer. A variety of extracellular membrane vesicles have been described, for instance microvesicles, ectosomes and a subtype called exosomes. The role of exosomes in tumour progression has been studied extensively in the last 10 years. In the present mini-review, we discuss our recent results, first showing the heterogeneity of the vesicles called exosomes and the probable existence of subpopulations of these exosomes, and secondly demonstrating that in vivo secretion of exosomes by some tumours can promote tumour progression, but that such a function cannot be generalized to all tumours and all exosomes.

The Role of Macrophages in Tumor Development

Macrophages constitute a large proportion of the immune cell infiltrate, which is present in many tumors. Activation state of macrophages is greatly influenced by their environment, leading to different macrophage subsets with diverse functions. Although previously regarded as potent immune cells that are capable of destroying tumor cells, recent literature focuses on the ability of macrophages to promote tumor development due to secretion of mediators, like growth and angiogenic factors. It is now becoming increasingly clear that a complicated synergistic relationship exists between macrophages and malignant cells whereby tumor cells can affect macrophage phenotype, and vice versa. As such, macrophages and their contribution in cancer development are currently subject of debate.