Interleukin-1 (IL-1) is a cytokine that is secreted by various cell types of the immune system such as macrophages, monocytes and dendritic cells, but also by fibroblasts and endothelial cells. It owes its name to the fact that it was the first cytokine to be discovered. The cytokine is produced in response to bacterial infections (its production is mainly mediated by LPS = important PAMP, which has been identified as an integral and essential component of the outer membrane of Gram-negative bacteria. The naming LPS = lipopolysaccharide refers to its chemical structure; it consists of a hydrophilic polysaccharide portion and a hydrophobic lipid A., an endotoxin of Gram-negative bacteria, stimulates).
Interleukin-1 has both local and general systemic effects, including the promotion of inflammatory processes in response to bacterial infections such as vasodilation, limb pain and fever. It also stimulates the production of prostaglandins by various cell types (muscles, epithelia, etc.), the production of other cytokines such as interleukin-2 and the activation and recruitment of other cells of the immune system. Specifically, interleukin-1 cytokines cause vasodilation of blood vessels (through prostaglandins), promoting the migration of immune cells such as macrophages and lymphocytes to the site of infection. IL-1 favors the expression of adhesion molecules in the cells of the endothelium of the blood vessels, the anchoring of leukocytes to the vessel walls and their migration into the tissue. Another ability of interleukin-1 cytokines is to contribute to the activation of T helper lymphocytes and to the maturation and clonal expansion of B lymphocytes. In systemic infections, the effect of interleukin-1 is comparable to TNF-alpha in that it stimulates the production of acute phase proteins in the liver.
In addition to stimulating inflammatory processes, interleukin-1 is able to trigger fever directly and autonomously even in the absence of other stimuli (bacterial antigens, see AMP - antimicrobialpeptides below) and is therefore referred to as an endogenous pyrogen . Interleukin-1 binds to specific receptors in the endothelial cells of the hypothalamus and appears to be able to "reset" its thermoregulation center. This leads to an increase in body temperature, a fever. Under febrile temperatures, the replication of bacteria and viruses decreases, while the immune response becomes more efficient.
Release of interleukin-1: DAMPs (DAMPs = acronym for "danger-associated molecular pattern", also known as alarmins are non-microbial pathogens that lead to the release of inflammatory mediators such as interleukin-1beta and interleukin-18 in the organism) or PAMPs (e.g. antimicrobial peptides) play a major role here. DAMPs/PAMPs are released by "stressed" cells, for example. Cell stress can be caused by infections but also by injuries, ischemia, hypoxia, acidosis and complement lysis. This results in necrosis or pyroptosis of the attacked cells. Intracellular components with damaged protein molecules enter the extracellular space. Due to their faulty structures (misfolding of proteins, oxidative changes in connection with the altered pH value), such pathological proteins are recognized by cells of innate immunity via their pattern recognition receptors (PRRs). They act as signaling devices for the immune system, which then reacts to them. A first step is the cleavage of the constitutively stored interleukin-1 alpha precursor molecule into its active form by a Ca2+-activated protease called calpain. The N-terminal 16 kDa cleavage product (ppIL-1 alpha) is cleaved and released. PpIL-1 alpha contains a nuclear localization sequence (NLS). This migrates into the cell nucleus and functions there as a transcription factor.
Inflammatory reactions without infection: Non-infectious inflammatory reactions, e.g. in ischemia, can also be initiated via the interleukin-1 receptor (IL-1R). IL-1 alpha stimulates the transcription and secretion of IL-1beta from monocytes. IL-1beta appears to be an amplifier of inflammation through the recruitment of macrophages and other inflammatory cells.