Glutathione is one of the most important and potent antioxidants. The development of pharmacological compounds that can either increase or decrease glutathione concentrations has allowed investigation into the role of glutathione in various biological processes, including immune responses. Recent findings have shown that glutathione not only affects certain factors involved in immunological processes but also modifies complex immune reactions such as fever. Until recently, it was not known why some patients do not develop fever during infection. Data suggest that fever induction is associated with oxidative stress; therefore, antioxidants such as glutathione can reduce pyrexia. Surprisingly, new studies have shown that low glutathione levels can also inhibit fever. In this review, we focus on recent advances in this area, with an emphasis on the role of glutathione in immune responses accompanied by fever. We describe evidence showing that disturbed glutathione homeostasis may be responsible for the lack of fever during infections. We also discuss the biological significance of the antipyretic effects produced by pharmacological glutathione modulators.

Chronic inflammation is a well-recognised tumour-enabling component, which includes bioactive molecules from cells infiltrating the tumour microenvironment and increases the risk of cancer progression. Since long-term use of the currently available anti-inflammatory drugs used in cancer therapy causes numerous side effects, the aim of this study was to investigate the effect of an extract isolated from the Coriolus versicolor fungus (CV extract) on HUVEC endothelial cells and MCF-7 breast cancer cells in a pro-inflammatory microenvironment mimicked by lipopolysaccharide (LPS). The cells were simultaneously stimulated with the LPS and CV extract. After co-treatment, the cell viability, generation of reactive oxygen species (ROS), wound-healing assay, production of the pro-inflammatory and pro-angiogenic factors (interleukin (IL) 6, IL-8, and metalloproteinase (MMP) 9)), as well as expression of Toll-like receptor (TLR) 4 and phosphorylated IκB (p-IκB) were evaluated. The results showed that the CV extract inhibited IL-6, IL-8, and MMP-9 production by the LPS-stimulated cells. This effect was accompanied by a decrease in TLR4 and p-IκB expression. The CV extract also had anti-migratory properties and induced a cytotoxic effect on the cells that was enhanced in the presence of LPS. The observed cytotoxicity was associated with an increase in ROS generation. We conclude that the CV extract possesses cytotoxic activity against cancer cells and endothelial cells and has the ability to inhibit the expression of the pro-tumorigenic factors associated with inflammation.

Coriolus versicolor (CV) is a common species from the Polyporaceae family that has been used in traditional Chinese herbal medicine for over 2000 years. Among well-described and most active compounds identified in CV are polysaccharopeptides, such as polysaccharide peptide (PSP) and Polysaccharide-K (PSK, krestin), which, in some countries, are already used as an adjuvant agent in cancer therapy. In this paper, research advances in the field of anti-cancer and anti-viral action of CV are analyzed. The results of data obtained in in vitro and in vivo studies using animal models as well as in clinical research trials have been discussed. The present update provides a brief overview regarding the immunomodulatory effects of CV. A particular focus has been given to the mechanisms of direct effects of CV on cancer cells and angiogenesis. A potential use of CV compounds in anti-viral treatment, including therapy against COVID-19 disease, has also been analyzed based on the most recent literature. Additionally, the significance of fever in viral infection and cancer has been debated, providing evidence that CV affects this phenomenon.

Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in synthesis and β-oxidation of other lipids, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein S-palmitoylation remains largely unknown. In this study we performed high-throughput proteomic analyses of a membrane-enriched fraction of murine liver to examine the influence of a palm oil-rich diet (HPD) on S-palmitoylation of proteins. HPD feeding for 4 weeks led to an accumulation of C16:0 and C18:1 fatty acids in livers which disappeared after 12-week feeding, in contrast to an accumulation of C16:0 in peritoneal macrophages. Parallel proteomic studies revealed that HPD feeding induced a sequence of changes of the level and/or S-palmitoylation of diverse liver proteins involved in fatty acid, cholesterol and amino acid metabolism, hemostasis, and neutrophil degranulation. The HPD diet did not lead to liver damage, however, it caused progressing obesity, hypercholesterolemia and hyperglycemia. We conclude that the relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, possibly including dynamic protein S-palmitoylation.

Fever-range hyperthermia (FRH) is utilized in chronic disease treatment and serves as a model for fever’s thermal component investigation. Macrophages, highly susceptible to heat, play a pivotal role in various functions determined by their polarization state. However, it is not well recognized whether this process can be modulated by FRH. To address this, we used two different macrophage cell lines that were treated with FRH. Next, to define macrophage phenotype, we examined their functional surface markers CD80 and CD163, intracellular markers such as inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), and the expression of interleukin-10 (IL-10) and tumor necrosis factor α (TNF-α). Additionally, in FRH-treated cells, we analyzed an expression of Toll-like receptor 4 (TLR-4) and its role in macrophage polarization. We also checked whether FRH can switch the polarization of macrophages in pro-inflammatory condition triggered by lipopolysaccharide (LPS). FRH induced M2-like polarization, evident in increased CD163, IL-10, and Arg-1 expression. Notably, elevated COX-2, TNF-α, and TLR-4 indicated potential pro-inflammatory properties, suggesting polarization towards the M2b phenotype. Additionally, FRH shifted lipopolysaccharide (LPS)-induced M1 polarization to an M2-like phenotype, reducing antimicrobial molecules (ROS and NO). In summary, FRH emerged as a modulator favoring M2-like macrophage polarization, even under pro-inflammatory conditions, showcasing its potential therapeutic relevance.

Endotoxin, a key component of Gram-negative bacterial membranes, remains a central focus in understanding host–pathogen interactions and immune modulation. In this review, we examine the multifaceted roles of endotoxin, with particular emphasis on how its structural variants modulate host immune recognition and inflammatory signalling. We explore the complex mechanisms by which endotoxin activates innate immune pathways and how these responses evolve under repeated or chronic exposure conditions. Special attention is given to the phenomenon of endotoxin tolerance, an adaptive reprogramming of immune cells that can profoundly alter inflammatory outcomes. While this tolerance serves as a protective mechanism against hyperinflammation, mounting evidence suggests that it may have a “dark side”, potentially impairing immune surveillance and promoting disease states such as cancer. We also discuss emerging clinical and therapeutic strategies that harness or counteract endotoxin-driven responses, from vaccine adjuvants to anti-sepsis interventions. By integrating recent findings from immunology, microbiology, and translational medicine, this review sheds light on the dual nature of endotoxin and its far-reaching implications for human health.