Possible Role of Pineal and Extra-Pineal Melatonin in Surveillance, Immunity, and First-Line Defense

Abstract

Melatonin is a highly conserved molecule found in prokaryotes and eukaryotes that acts as the darkness hormone, translating environmental lighting to the whole body, and as a moderator of innate and acquired defense, migration, and cell proliferation processes. This review evaluates the importance of pineal activity in monitoring PAMPs and DAMPs and in mounting an inflammatory response or innate immune response. Activation of the immune–pineal axis, which coordinates the pro-and anti-inflammatory phases of an innate immune response, is described. PAMPs and DAMPs promote the immediate suppression of melatonin production by the pineal gland, which allows leukocyte migration. Monocyte-derived macrophages, important phagocytes of microbes, and cellular debris produce melatonin locally and thereby initiate the anti-inflammatory phase of the acute inflammatory response. The role of locally produced melatonin in organs that directly contact the external environment, such as the skin and the gastrointestinal and respiratory tracts, is also discussed. In this context, as resident macrophages are self-renewing cells, we explore evidence indicating that, besides avoiding overreaction of the immune system, extra-pineal melatonin has a fundamental role in the homeostasis of organs and tissues.

The Role of Melatonin in Chronic Kidney Disease and Its Associated Risk Factors: A New Tool in Our Arsenal?

“…Although the pineal gland is described as the primary site for MT production, MT-synthesizing enzymes have been detected in various tissues and cell types, indicating the extrapineal MT synthesis. It should be noted that under inflammatory conditions, such as arterial hypertension, DM, and CKD, pineal nocturnal MT synthesis is suppressed and its extrapineal production by immune cells is augmented [9].…”

The role of melatonin in the development of postmenopausal osteoporosis

“…As the precursors of osteoclasts, monocyte-derived macrophages are the direct link between the immune and skeletal systems (Yang and Liu, 2021). Melatonin inhibits the osteoclastogenesis and migration of macrophages to suppress inflammation-mediated bone resorption (Markus et al, 2021;Kim et al, 2022). Melatonin also acted on other immunocytes to modulate bone metabolism indirectly.…”

The role of melatonin in the formation of tuberculotic inflammation, forecast regarding the influence on the effectiveness of treatment in the conditions of the COVID­-19 pandemic (literature review)

“…Мелатонін має багато рецепторів, які містяться майже в усіх системах організму, зокрема на клітинах імунної системи [29]. Хоча цей гормон виробляється переважно епіфізом, дослідження показали, що мелатонін також синтезується в кістковому мозку [50], тимусі [38], лімфоцитах [14] та різних клітинах шлунково-кишкового тракту, кожна з яких впливає на імунну функцію [31,36].…”

“…Вважають, що мелатонін завдяки прооксидантним властивостям захищає організм від інфекцій [15,31]. Проте є повідомлення про вплив мелатоніну на життєздатність патогенних бактерій, зокрема МБТ, та інші агенти, наприклад, ізоніазид, що можуть залежати від утворення вільних радикалів [26].…”