No abstract

Chronic inflammation may not begin with local tissue disorders, such as hypoxia, but with the accumulation of critically activated macrophages in one site. The purpose of this review is to analyze the data reported in the scientific literature on the features of the functions of macrophages and their contributions to the development of pathology in various tissues during aseptic inflammation in obese subjects. In individuals with obesity, increased migration of monocytes from the peripheral blood to various tissues, the proliferation of resident macrophages and a change in the balance between alternatively activated anti-inflammatory macrophages (M2) and pro-inflammatory classically activated macrophages (M1) towards the latter have been observed. The primary cause of some metabolic pathologies has been precisely identified as the recruitment of macrophages with an altered phenotype, which is probably typical for many other pathologies. Recent studies have identified phenotypes, such as metabolically activated M (MMe), oxidized (Mox), hemoglobin-related macrophages (Mhem and MHb), M4 and neuroimmunological macrophages (NAM, SAM), which directly and indirectly affect energy metabolism. The high heterogeneity of macrophages in tissues contributes to the involvement of these cells in the development of a wide range of immune responses, including pathological ones. The replenishment of tissue-specific macrophages occurs at the expense of infiltrating monocyte-derived macrophages (MoMFs) in the pathological process. The origin of MoMFs from a general precursor retains their common regulatory mechanisms and similar sensitivity to regulatory stimuli. This makes it possible to find universal approaches to the effect on these cells and, as a consequence, universal approaches for the treatment of various pathological conditions.

Interleukin-8 (IL-8, CXCL8) is one of the main chemokines that stimulates the migration of neutrophils, monocytes and lymphocytes into the inflammatory focus. The aim of this study was to investigate the direct influence of IL-8 on the functionality of human monocytes/macrophages (Mc (Mph)) upon their activation by lipopolysaccharide (LPS). CD14+ cells were isolated from blood mononuclear cells (MNCs) by positive magnetic separation. Surface markers (CD16, CD119, CD124, CD197) in Mc (Mph) cultures were determined by flow cytometry, while IL-10, IL-6, IL-1 ß and tumor necrosis factor-а (TNF-а) concentrations in cell supernatants by solid-phase enzyme-linked immunosorbent assay. IL-8 was found to be capable of significantly reducing the number of CD16+ (FcyRIII) cells among activated Mc (Mph). At the same time, IL-8 detectably increased the number of cells expressing CD1 1 9 (receptor to interferon-y) and CD197 (CCR7), reducing the number of cells carrying CD124 (receptor to IL-4). In addition, IL-8 was able to enhance the secretion of IL-6 and IL-1 ß by activated Mph cells, without significantly affecting the production of TNF-а and IL-10. The data obtained indicate the ability of IL-8 to directly favor the pro-inflammatory activity of Mph cells.

Immunoglobulin-G4-related disease (IgG4-RD) is a chronic immunomediated pathology of different organs of local or systemic nature, which has been established as a separate clinical entity in the early 2000s and is characterized by storiform fibroid inflammation of the affected tissues, their increase, and elevated serum immunoglobulin-G4 (IgG4) levels. The most common manifestations of the disease are major salivary and lacrimal gland enlargement, lymphadenopathy and type 1 autoimmune pancreatitis (AIP1), however, other organs may be also involved (the thyroid, eyes, meninges, heart, lungs, kidneys, aorta, upper airways, mesentery, etc.). The effectiveness of treatment of IgG4-RD, as well as other pathological conditions, is also determined by the timely diagnosis. However, the latter is complicated due to the variety of clinical manifestations and rather variable diagnostic criteria. It is necessary to constantly update the evidence-based knowledge and diagnostic algorithms within this pathology in order to overcome the difficulties, and involve immunologists, endocrinologists, pathologists and specialists in other spheres. This review provides information about the etiology, pathogenesis, and current methods of diagnosis and treatment of IgG4-related diseases, as well as examples of some manifestations of IgG4-RD that an endocrinologist may face in practice.

No abstract