Inflammation- Definition, causes and its types

II.  Chronic Inflammation

It may start slowly and take many days or weeks to manifest, persist for a long period or start as an acute inflammation that does not resolve or becomes disordered. In contrast with acute inflammation, which is distinguished by vascular changes, edema, and a predominantly neutrophilic infiltrate, chronic inflammation is characterized by a different set of reactions:

• Infiltration with mononuclear cells, including macrophages, lymphocytes, and plasma cells .
• Tissue destruction, largely induced by the products of the inflammatory cells.
• Repair, involving new vessel proliferation (angiogenesis) and fibrosis.

Chronic inflammation may arise in the following settings:

• Persistent infections by microbes that are difficult to eradicate.

 These include Mycobacterium tuberculosis, Treponema pallidum (the causative organism of syphilis), and certain viruses and fungi, all of which tend to establish persistent infections and elicit a T lymphocyte–mediated immune response called delayed-type hypersensitivity.

• Immune-mediated inflammatory diseases (hypersensitivity diseases)

 Diseases that are caused by excessive and inappropriate activation of the immune system are increasingly recognized as being important health problems. Under certain conditions, immune reactions develop against the affected person’s own tissues, leading to autoimmune diseases. In such diseases, autoantigens evoke a self-perpetuating immune reaction that results in tissue damage and persistent inflammation. Autoimmunity plays an important role in several common and debilitating chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Immune-mediated diseases may show morphologic patterns of mixed acute and chronic inflammation because they are characterized by repeated cycles of inflammation. Since, in most cases, the eliciting antigens cannot be eliminated, these disorders tend to be chronic and intractable.

• Prolonged exposure to potentially toxic agents

Examples are nondegradable exogenous materials such as inhaled particulate silica, which can induce a chronic inflammatory response in the lungs , and endogenous agents such as cholesterol crystals, which may contribute to atherosclerosis

• Mild forms of chronic inflammation may be important in the pathogenesis of many diseases that are not conventionally thought of as inflammatory disorders. Such diseases include neurodegenerative disorders such as Alzheimer disease, atherosclerosis, metabolic syndrome and the associated type 2 diabetes, and some forms of cancer in which inflammatory reactions promote tumor development. In many of these conditions the inflammation may be triggered by recognition of the initiating stimuli by the inflammasome. The role of inflammation in these conditions is discussed in the relevant chapters.

Cells involved in Chronic Inflammation

The cellular components of chronic inflammatory responses are recruited from the circulation (macrophages, lymphocytes, plasma cells, dendritic cells and eosinophils) and affected tissues (fibroblasts, vascular endothelial cells).

Macrophages

They are tissues cells derived from circulating blood monocytes after their emigration from the bloodstream. Monocytes arise from precursors in the bone marrow and circulate in the blood for only about a day. Under the influence of adhesion molecules and chemokines, they migrate to a site of injury within 24 to 48 hours after the onset of acute inflammation. When monocytes reach the extravascular tissue, they undergo transformation into macrophages, which are somewhat larger and have a longer lifespan and a greater capacity for phagocytosis than do blood monocytes. They are normally scattered in most connective tissues and are also found in organs like liver where they are called as Kupffer cells, spleen and lymph nodes where they are called as sinus histiocytes, central nervous system and lungs. Together these cells constitute the so called mononuclear phagocyte system. Activated macrophages and their cytokines are central to initiate inflammation and prolonging responses that lead to chronic inflammation. Macrophages produce inflammatory and immunological mediators, and regulate reactions leading to chronic inflammation. Macrophages produce inflammatory and immunological mediators, and regulate reactions leading to chronic inflammation. They also regulate lymphocyte responses to antigens and secret other mediators that modulate fibroblast and endothelial cell proliferation and activities.

Macrophages have several critical roles in host defense and the inflammatory response.

• Macrophages, like the other type of phagocyte, the neutrophils, ingest and eliminate microbes and dead tissues. Because macrophages respond to activating signals from T lymphocytes, they are the most important phagocytes in the cell-mediated arm of adaptive immune responses.
• Macrophages initiate the process of tissue repair and are involved in scar formation and fibrosis.
• Macrophages secrete mediators of inflammation, such as cytokines (TNF, IL-1, chemokines, and others) and eicosanoids. These cells are therefore central to the initiation and propagation of all inflammatory reactions.
• Macrophages display antigens to T lymphocytes and respond to signals from T cells, thus setting up a feedback loop that is essential for defense against many microbes by cell mediated immune responses. The same bidirectional interactions are central to the development of chronic inflammatory diseases. The roles of cytokines in these interactions are discussed later.