Some microbial infections can result in chronic inflammation, most especially infections with organisms such as metazoan parasites, fungi and mycobacteria. Moreover, autoimmune diseases, transplantation, and allergy can induce chronic inflammation. Generally, chronic inflammation occurs if acute inflammation fails to resolve on its own. Acute inflammation will fail to resolve if the inciting stimulus persists. Chronic inflammation ensues when the inflammatory response goes on for weeks or months.
Infective agents that induce chronic inflammation are intracellular pathogens mostly.
Chronic inflammation results from the continued presence of the inciting agent. It may be the continued presence of a pathogen as in the case of pathogen-induced chronic inflammation. Perhaps it could result from the continued presence of self-antigens as in the case of autoimmune diseases. Therefore, the continued presence of the inciting agent in the host causes the persistent activation of the immune system against the agent consequently resulting in chronic inflammation.
What can induce chronic inflammation?
1. Chronic infections: some infectious organisms are resistant to killing and elimination mechanisms of the body. Infections with such organisms tend to result in chronic inflammation.
2. Viral infections
3. Persistent injurious stimuli
4. Autoimmune disease: chronic inflammation is arguably a common component of autoimmune diseases. Since the immune reaction is against a host antigen (which is always present), the inflammation definitely is chronic.
Chronic inflammatory cells
The histology of tissues undergoing chronic inflammation mostly reveals two cell types: macrophages and lymphocytes. The most basic forms of chronic inflammation have lymphocytes as the most abundant cells with relatively lesser number of macrophages. Mostly, this occurs in viral infections, in which the virus out-lives the acute phase.
The presence of plasma cells at the site of inflammation tells two things:
1. The inflammation is chronic since it takes at least 2 weeks to generate a good number of plasma cells
2. The inflammation has an infectious cause since the aggregation of plasma cells indicates that the body needs abundant antibodies at the site of inflammation
In granulomatous inflammation, the predominant cell types are macrophages. The inciting agent is a persistent antigen mostly. During the development of a granulomatous chronic inflammation, antigens derived from the invading microbe induce the production of various chemokines. These chemokines attract monocytes from blood recruiting them to the site of infection.
Once they arrive at the infected tissue, blood monocytes transform into tissue macrophages. The macrophages gather round the infected area completely encircling the area.
If the macrophages are unable to kill and eradicate the foreign antigen, few macrophages fuse to form a single multinucleated giant cell. Over a considerable time, giant cells form aggregates of closely packed cells that encircle the infecting microbe completely.
In most cases, debris fills the central core of the granuloma; a ring of differentiated macrophages, which in turn is surrounded by lymphocytes and fibroblasts, surrounds this central core.
The presence of multinucleated giant cells indicates that ordinary macrophages were unable to rid the body of the infecting agents, making it necessary for them to ‘gang up’.
Acute vs. chronic inflammation
In contrast to acute inflammation, where neutrophil accumulation is the defining feature; in chronic inflammation the accumulation and resultant activation of large numbers of macrophages and lymphocytes form the defining feature. In acute inflammation, neutrophils are the main white blood cells recruited from blood to the site of the reaction whereas monocytes are the principal cells recruited from blood during chronic inflammation.
In addition to large numbers of macrophages, enormous amounts of lymphocytes are present in sites of chronic inflammation. Together these cells of the immune system fight and eliminate the inciting agent.
During chronic inflammation, activated macrophages release nitrogen intermediates, hydrolytic enzymes, and reactive oxygen species, which act on host tissues causing varying degrees of damage to host tissues.
Unlike acute inflammation, chronic inflammation causes so many problems in the patient. Consequently, anti-inflammatory drugs are given to patients with chronic inflammation to help control the inflammatory response.
The most essential difference between acute and chronic inflammation is the time factor. By definition, chronic inflammation is inflammation that persists for weeks to months whereas acute inflammation resolves within few hours to few days.
Characteristically, acute inflammation is exudative-oozing of tissue fluid- whereas chronic inflammation does not ooze. Exudation is not as obvious in chronic inflammation as it is in the acute reaction. The observable characteristic feature seen in sites of chronic inflammation is either the collection of pus and other tissue fluid or the proliferation of affected tissue. (The tissue proliferation may result in formation of inflammatory lesion called granuloma).
Principal cells that participate in chronic inflammation tend to produce substances that deposit new tissue such as collagen and form new blood vessels. Fibroblasts are cells that produce collagen; there is prominent multiplication and growth of fibroblast in sites of chronic inflammation. This phenomenon called fibroplasia is responsible for the increased deposit of collagen in sites of chronic inflammation. In chronic inflammation, there is pronounced angiogenesis (formation of new blood vessels) and resultant neovascularization of tissues. Thus, the most significant vascular changes that occur during acute inflammation are vasodilation together with increased vascular permeability whereas that of chronic inflammation is angiogenesis.
Because of neovascularization and fibroplasia, areas of the body affected by chronic inflammation tend to swell forming a solid and firm mass of tissue. Fibrosis is the most common sign of chronic inflammation; actually, the formation of fibrosis (scar) is the most reliable indicator that the inflammatory reaction is chronic.
Generally, in chronic inflammation tissue destruction and attempts at repair of destroyed tissues seem to be happening at the same time.
The tissue redness and heat that occur in acute inflammation are not prominent features of chronic inflammation.