Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. In such a setting, the establishment of an effective therapy to treat this condition has been elusive, perhaps because the experimental treatments have been conceived to block just one of the many pathogenic pathways of the disease, or because they thwart the tissue-repairing phase of the syndrome. Either way, we think that a discussion about the pathophysiology of the disease and the mechanisms of action of some drugs may shed some clarity on the topic.

Macrophages are innate immune cells derived from monocytes, which, in turn, arise from myeloid precursor cells in the bone marrow. Macrophages have many important roles in the innate and adaptive immune response, as well as in tissue homeostasis. Two major populations have been defined: The classically activated macrophages that respond to intracellular pathogens by secreting proinflammatory cytokines and reactive oxygen species and alternatively activated macrophages which are induced during Th2 responses displaying anti-inflammatory activities. Both macrophage populations are central players in diabetes, the first one triggering inflammatory responses which initiates insulitis and pancreaticβcell death during type 1 diabetes, whereas the second population decreases hyperglycemia, insulitis, and inflammation in the pancreas, thereby negatively regulate type 1 diabetes. Obesity is an important factor in the development of type 2 diabetes; classically activated macrophages are a dominant cell population involved in the establishment of the inflammatory profile, insulin resistance, and activation of inflammatory signals during the development and progression of this disease. In contrast, alternatively activated macrophages regulate the release of proinflammatory cytokines, attenuating adipose tissue inflammation. Here, we review the advantages and disadvantages of these two macrophage populations with regard to their roles in types 1 and 2 diabetes.

Taenia crassicepsis a cestode parasite of rodents (in its larval stage) and canids (in its adult stage) that can also parasitize immunocompromised humans. We have studied the immune response elicited by this helminth and its antigens in mice and human cells, and have discovered that they have a strong capacity to induce chronic Th2-type responses that are primarily characterized by high levels of Th2 cytokines, low proliferative responses in lymphocytes, an immature and LPS-tolerogenic profile in dendritic cells, the recruitment of myeloid-derived suppressor cells and, specially, alternatively activated macrophages. We also have utilized the immunoregulatory capabilities of this helminth to successfully modulate autoimmune responses and the outcome of other infectious diseases. In the present paper, we review the work of others and ourselves with regard to the immune response induced byT. crassicepsand its antigens, and we compare the advances in our understanding of this parasitic infection model with the knowledge that has been obtained from other selected models.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400–800 mg or > 800 mg), either at the viral (1–7 days post-symptom onset), early inflammatory (8–15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37–4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4–15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400–800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Antimicrobial resistance (AR) is one of the most important public health challenges worldwide as it represents a serious complication that is able to increase the mortality, morbidity, disability, hospital stay and economic burden related to infectious diseases. As such, the spread of AR–pathogens must be considered as an emergency, and interdisciplinary approaches must be undertaken in order to develop not only drugs, but holistic strategies to undermine the epidemic and pathogenic potentials of multi-drug resistant (MDR) pathogens. One of such approaches has focused on the use of antimicrobial nanoparticles (ANPs), as they have demonstrated to possess strong antimicrobial effects on MDR pathogens. On the other hand, the ability of bacteria to develop resistance to such agents is minimal. In this way, ANPs may seem a good choice for the development of new drugs, but there is no certainty about their safety, which may delay its translation to the clinical setting. As MDR pathogens are quickly becoming more prevalent and drug development is slow and expensive, there is an increasing need for the rapid development of new strategies to control such agents. We hereby explore the possibility of designing ANP-based devices such as surgical masks and fabrics, wound dressings, catheters, prostheses, dentifrices, water filters, and nanoparticle-coated metals to exploit the potential of such materials in the combat of MDR pathogens, with a good potential for translation into the clinical setting.

Relapsing-remitting multiple sclerosis, the most common form, is characterized by acute neuroinflammatory episodes. In addition to continuous disease-modifying therapy, these relapses require treatment to prevent lesion accumulation and progression of disability. Intravenous methylprednisolone (1–2 g for 3–5 days) is the standard treatment for relapses. However, this treatment is invasive, requires hospitalization, leads to substantial systemic exposure of glucocorticoids, and can only reach modest concentrations in the central nervous system (CNS). Intranasal delivery may represent an alternative to deliver relapse treatment directly to the CNS with higher concentrations and reducing side effects. Histopathological analysis revealed that intranasal administration of methylprednisolone to mice with experimental autoimmune encephalomyelitis (EAE) suppressed the neuroinflammatory peak, and reduced immune cell infiltration and demyelination in the CNS similarly to intravenous administration. Treatment also downregulated Iba1 and GFAP expression. A similar significant reduction of IL-1β, IL-6, IL-17, IFN-γ, and TNF-α levels in the spinal cord was attained in both intranasal and intravenously treated mice. No damage in the nasal cavity was found after intranasal administration. This study demonstrates that intranasal delivery of methylprednisolone is as efficient as the intravenous route to treat neuroinflammation in EAE.