How many systemic reactions in inflammation?

How many systemic reactions in inflammation?

We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

I have this sentence in my notes

Inflammation consists of two local reactions and one systemic reactions.

which is difficult for me to accept. Two local reactions are vascular and cellular. I think there are two systemic reactions too:

  • White blood cell response
  • Acute-phase response

How many systemic reactions there are in the inflammation?

There are two systemic reactions in inflammation too: mediated by leucocytes and acute-phase response (proteins).

Inflammation can be either short-lived (acute) or long-lasting (chronic). Acute inflammation goes away within hours or days. Chronic inflammation can last months or years, even after the first trigger is gone. Conditions linked to chronic inflammation include:

Some types of arthritis are the result of inflammation, such as:

Other painful conditions of the joints and musculoskeletal system that may not be related to inflammation include osteoarthritis, fibromyalgia, muscular low back pain, and muscular neck pain.

Periodontal Disease, Systemic Inflammation and the Risk of Cardiovascular Disease

Periodontal and cardiovascular disease are both major health issues. Poor oral health has long been associated with the development of systemic diseases, with the typical example being the risk of endocarditis posterior to dental procedures. Through the years, the association of periodontal disease with other non-infectious systemic diseases has been brought to attention. One of the most interesting associations is the one that exists with the development of cardiovascular disease. Many studies, including systematic reviews and meta-analyses, suggest an important association between periodontal disease and ischaemic heart disease, cerebrovascular disease, heart failure, atrial fibrillation and peripheral artery disease. Among the proposed mechanisms of this relationship, systemic inflammation appears to play a major role. Evidence suggests that periodontal inflammation triggers a systemic inflammatory state that, added to the damage mediated by antibodies that cross react between periodontal pathogens and components of the intimal wall, and the direct lesion of the intima by bacteria entering the circulation, promotes atheroma plaque development and progression. There are other studies that show a clear relationship between periodontal disease severity, elevations of inflammatory markers, and the presence of atherosclerosis. Here, we give a review of the available evidence supporting this association, and the possible mechanisms involved.

Keywords: Atherosclerosis Cardiovascular disease Periodontal disease Systemic inflammation.

Late-onset inflammatory adverse reactions related to soft tissue filler injections

An ever-increasing number of persons seek medical solutions to improve the appearance of their aging skin or for aesthetic and cosmetic indications in diverse pathological conditions, such as malformations, trauma, cancer, and orthopedic, urological, or ophthalmological conditions. Currently, physicians have many different types of dermal and subdermal fillers, such as non-permanent, permanent, reversible, or non-reversible materials. Despite the claims of manufacturers and different authors that fillers are non-toxic and non-immunogenic or that complications are very uncommon, unwanted side effects do occur with all compounds used. Implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions, including inflammation, thrombosis, and excessive fibrosis. Usually, these adverse reactions are associated with the accumulation of large numbers of mononuclear cells. The adverse reactions related to fillers comprise a broad range of manifestations, which may appear early or late and range from local to systemic. Clinicians should be aware of them since the patient often denies the antecedent of injection or is unaware of the material employed. Most of these adverse effects seem to have an immunological basis, the fillers acting more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies management of both acute and systemic reactions is often difficult, and requires anti-inflammatory and occasionally immunosuppressive therapy. The clinical, pathological, and therapeutic aspects of inflammatory and immune-mediated late-onset adverse reactions related to soft tissue filler injections are thoroughly reviewed herein.

Inflammation: Meaning and Purpose | Cell Injury | Organisms| Microbiology

In this article we will discuss about:- 1. Meaning and Purpose of Inflammation 2. Tissue Changes Associated with Inflammation 3. Mediators of Inflammatory Reactions 4. Leucocyte Recruitment and Activation 5. Leucocyte Functions during Inflammation 6. Healing and Tissue Repair.

Meaning and Purpose of Inflammation:

Inflammation is the body’s normal response to tissue injury, although it can sometimes lead to pathological tissue damage, including that seen in the hypersensitivity reactions.

The purpose of inflammation is:

1. To contain and control infection or injury

3. To initiate healing and tissue repair

Inflammation represents a complex interaction of many components including blood vessels, tissue-derived mediators, while cells (leucocytes), fibroblasts, endothelial cells, epithelium, the coagulation and fibrinolytic systems, the kinin system and the component system.

Inflammation is characterized by local tissue signs, first described in about 30 BC by Celsus, which are tumour (swelling), rubor (redness), calor (heat) and dolor (pain). Systemic effects include fever, increased production of leucocytes by the bone marrow (leucocytosis) and increased synthesis of some plasma proteins by the liver. The tissue changes associated with the inflammation.

Tissue Changes Associated with Inflammation:

Inflammatory responses are classified as acute or chronic reactions, depending upon the histological and morphological features, although these are not always exclusive. The nature of the inflammatory response and its detailed appearance depend on the type of injury and the tissue involved.

For instance, acute inflammation in the skin has a different macroscopic appearance to that in internal organs or mucous membranes. Chronic inflammation sometimes follows acute inflammation if, for instance, the acute response fails to eliminate a pathogen. However, chronic inflammation can occur without an acute response.

i. Acute Inflammation:

The acute inflammatory response occurs rapidly (minutes to hours) after injury or infection. Initially, there is dilation of small blood vessels (venules and arterioles) with an increased local blood flow (hyperaemia), which then decreases or stops (stasis). The vessels become more permeable, leading to movement of blood plasma and platelets into the tissues (this is often referred as a serous exudate), causing oedema (an excess of intercellular fluid in the tissues).

A serous exudate below the epidermis is what causes a blister. Fibrinogen in the exudate is converted to fibrin, which is deposited and helps to localize tissue damage and control bleeding. Blood cells, especially neutrophils, migrate into the tissue. Sometimes, typically in response to pyogenic (pus-forming) bacterial infection, a purulent exudate or pus is formed, consisting of dead cells, neutrophils and bacteria.

When large numbers of neutrophils are present the pus appears yellow or green, because of the presence of myeloperoxidase, a green-coloured protein in neutrophil granules. Localized pus accumulation causes an abscess.

ii. Chronic Inflammation:

Chronic inflammation, lasting from weeks to years, may result from unresolved or recurrent acute inflammation alternatively it may follow exposure to insoluble agents, foreign bodies, intracellular pathogens (e.g. Mycoabacterium tuberculosis or M. Leprae) or unknown aetiological factors, as in rheumatoid arthritis. Whereas the cellular infiltration in actue inflammation consists mainly of neutrophils, in chronic inflammation it is composed of a mixed cell population including macrophages.

The macrophages are derived from blood monocytes which migrate to the site of inflammation, become activated and proliferate. Lymphocytes and plasma cells are usually also present at the sites of chronic inflammation. In some forms of chronic inflammation (e.g. tuberculosis) granulomas are formed.

These consist of collections of epithelioid (epithelial-like) macrophages and lymphocytes, sometimes with much necrotic tissue. Often these necrotic granulomas have the appearance of ‘soft cheese’ and this has led to the alternative designation of ‘caseating granulomas’. The epitheloid macrophages are sometimes very large, with multiple nuclei and are often referred to as giant cells.

Mediators of Inflammatory Reactions:

The inflammatory process is initiated, maintained and controlled by many factors, which often have multiple and interacting effects.

Vasoactive Amines:

The early vasodilation and increased vascular permeability of acute inflammation are caused largely by the release of vasoactive amines such as histamine and 5-hydroxytryptamine (serotonin). These are secreted by a variety of cells including platelets, mast cells and basophils.

Arachidonic Acid Metabolites:

Arachidonic acid metabolites are pro-inflammatory factors which are expressed early, are short-­lived and have a wide range of activities. Prostaglandins cause vasodilation and pain thromboxanes cause platelet aggregation and vasoconstriction. Leukotrienes increase vascular permeability and leukotriene B4 (LTB4) is a chemotactic and activating factor for leucocytes, especially neutrophils. Chemotaxis is the process by which cells, for example neutrophils are attracted to sites of injury or infection by the release of a specific chemical agent.

Coagulation, Fibrinolytic, Kinin and Complement Systems:

The serous exudate at an inflammatory site contains the components of these systems, which interact and co-activate through a number of initiation stimuli. Thus, activation of Hageman factor (factor XII) of the coagulation system by surface active agents such as damaged connective tissues or microbial components, results in the conversion of fibrinogen to fibrin through the activation of several proteinases including thrombin.

Hageman factor also activates the kinin system, which results in the production of the vasoactive peptide bradykinin from the precursor’s prekallikrein and kininogen. The complement system, like the clotting/fibrinolytic and kinin systems, includes proteolytic enzyme activities in a cascade of events.

Because all these systems rely on the proteolytic activation of latent pro-enzymes (zymogens), there is often cross- activation. In addition, they all contain positive feedback loops which amplify the activation of each system. Complement is activated through the classical pathway by antibodies attached to a target pathogen, or through the alternate pathway by contact with a variety of agents, including bacteria.

The products of complement activation are designed largely to eliminate pathogens and include the following:

1. The release of anaphylatoxins, the small peptides derived from the cleavage of complement factors C3, C4 and C5. These peptides initiate increased blood vessel permeability and smooth muscle contraction, probably by causing histamine release from mast cells. In addition, C5a is a chemotactic factor and an activator of neutrophils.

2. Production of opsonins. Some products of activated complement factors e.g. (C3b) on pathogen surfaces stimulate phagocytosis by effector cells such as neutrophils and macrophages.

3. Lysis of cells by the formation of the lytic or membrane attack complex (MAC) of complement proteins on the target cell membrane.

Cytokines (including the interleukins, colony-stimulating factors, and tumour necrosis factors) are proteins produced by many cell types. A cell responds to cytokines for which it bears specific surface receptors the response depends on the concentration of the cytokine and the numbers or ‘affinity status’ of the receptors.

Cytokines modulate a large range of tissue functions, including chemotaxis and activation of inflammatory cells (e.g. leucocytes), morphogenesis, differentiation, proliferation, apoptosis, haemopoiesis and metabolism. Some cytokines activate cell functions directly, Others ‘prime’ cells, making them more sensitive to other stimuli. Cytokines should not be viewed as acting in isolation cytokines affect cells in cascades or networks.

Leucocyte Recruitment and Activation during Inflammation:

Cell Recruitment:

Changes in blood flow during acute inflammation favour the conditions for the first stage in migration of leucocytes from the blood to the tissues. Cell migration is selective since particular leucocytes are seen in different forms and stages of inflammation. The first stage in migration of blood cells from the blood to the tissue is adherence to the endothelium (margination or pavementing).

Vascular endothelium expresses receptors for adhesion molecules present on the leucocyte surface. The expression of specific receptors on endothelium is induced by the presence of inflammatory mediators.

The process of cell adhesion to endothelium and migration is now recognized as representing an adhesion cascade, which has the following four distinct stages:

Tethering, where leucocytes ‘roll’ along the vessel wall, being slowed or ‘tethered’ by low-affinity receptors called selectins L-selectin is expressed constitutively on leucocytes E-selectin and P-selectin and expressed on the endothelial cells when activated by cytokines.

Triggering involves the induction of adhesion molecules, known as integrins, on the leucocytes following their activation by complement proteins, bacterial products and a variety of cytokines, including platelet-activating factor and interleukin-8 (IL-8).

Strong adhesion, where integrins on the leucocytes bind strongly to endothelial cells. Strong adhesion is mediated by activation of the leucocytes and endothelium.

Migration of the leucocytes through endothelium, a process known as diapedesis. This is mediated by chemotactic factors including – LTB4, bacterial products such as formylated peptides (e.g. frmyl-met-leu-phe), complement peptides, chemokines and soluble peptides derived from damaged connective tissue constituents such as elastin, collagen and laminin. Many chemotactic factors also ‘activate’ leucocyte functions such as phagocytic activity and production of the respiratory burst.

The importance of cell recruitment during inflammation is illustrated by deficiencies such as leucocyte adherence deficiency (LAD), where components of adhesion molecules are absent or reduced, resulting in recurrent infections in the affected individual.

Leucocyte Functions during Inflammation:

Lymphocytes recruited during chronic inflammation contribute to the specific immunological component of pathogen elimination. Neutrophils and macrophages are phagocytic cells, capable of engulfing micro-organisms and, particularly in the case of macrophages, apoptotic or damaged cells and non-living particulate material. Phagocytosis is enhanced if the target is coated by antibodies (opsonized), complement proteins, or both. Phago­cytes have receptors for immunoglobulin (Ig) and complement.

Following their activation phagocytic cells produce a respiratory (oxidative) burst in which the membrane-bound NADPH-oxidase system produces reactive oxygen intermediates such as superoxide radicals (O – 2), hydrogen peroxide, hypochlorous acid and chloramines. These oxidative products are toxic to micro-organisms.

Individuals with chronic granulomatous disease suffer from recurrent infections because their cells cannot produce these oxidative products. Phagocytosed material is enclosed in a phagocytic vacuole which fuses with lysosomes to form phagolysosomes.

Lysosomes contain proteins and peptides which create ‘holes’ in the membranes of phagocytosed cells, causing lysis, and enzymes which can degrade peptides and proteins, carbohydrates and lipids. Thus there is complete degradation of phagocytosed organic material. Macrophages, eosinophils and mast cells also secrete enzymes and proteins that are damaging to foreign organisms and other cells.

Healing and Tissue Repair of Inflammation:

The main purpose of healing is to replace damaged tissue with functional cells, a process involving migration, proliferation and differentiation of surviving or nearby cells, contraction of the wound by myofibroblasts and production of appropriate connective tissues by cells including fibroblasts and chondrocytes.

Healing begins with the proliferation of fibroblasts and small blood vessels (producing so called granulation tissue). The success of regeneration depends on the type, degree and duration of inflammation and the integrity of remaining tissue.

Some tissues, such as skin and liver, regenerate relatively well whereas others (e.g. nervous tissue) do not. In the absence of regeneration, functional tissue is replaced by fibrotic (scar) tissue composed of large amounts of connective tissue proteins, especially collagen.

The healing process is mediated by a number of hormones, cytokines and growth factors, (including platelet-derived growth factor, epidermal growth factor, and transforming growth factors α and β) which interact in complex networks. They can act in synergy and some are inhibitory.

The resolution of the inflammatory process depends on the removal of the initial insult and changes in the pattern of mediators from those which are pro-inflammatory to those which induce healing. Remaining inflammatory cells appear to undergo apoptosis and are recognized and phagocytosed by macrophages.

If the inflammation is severe, it can cause general reactions in the body. These may include the following signs and symptoms:

A very rare but dangerous complication of an infection is called septicemia (blood poisoning). The possible signs of this complication include chills, feeling very ill, and a very high fever.

Septicemia may occur if bacteria multiply quickly in a certain part of the body and then a lot of them suddenly enter the bloodstream. This can happen if the body isn’t able to fight the infection locally, if the germs are very aggressive, or if the immune system is very weak. Septicemia is a medical emergency and needs to be treated by a doctor as soon as possible.

Immune Response

When an infection develops, the immune system also responds by producing several substances and agents that are designed to attack the specific invading microorganisms (see Acquired Immunity). Examples are

Killer T cells (a type of white blood cell) that can recognize and kill the invading microorganism

Antibodies that target the specific invading microorganism

Antibodies attach to and immobilize microorganisms. They kill them outright or help neutrophils target and kill them.

How well the immune system defends the body against each microorganism depends partly on a person's genetic make-up.


Inflammation is the immune system's response to harmful stimuli, such as pathogens, damaged cells, toxic compounds, or irradiation [1], and acts by removing injurious stimuli and initiating the healing process [2]. Inflammation is therefore a defense mechanism that is vital to health [3]. Usually, during acute inflammatory responses, cellular and molecular events and interactions efficiently minimize impending injury or infection. This mitigation process contributes to restoration of tissue homeostasis and resolution of the acute inflammation. However, uncontrolled acute inflammation may become chronic, contributing to a variety of chronic inflammatory diseases [4].

At the tissue level, inflammation is characterized by redness, swelling, heat, pain, and loss of tissue function, which result from local immune, vascular and inflammatory cell responses to infection or injury [5]. Important microcirculatory events that occur during the inflammatory process include vascular permeability changes, leukocyte recruitment and accumulation, and inflammatory mediator release [2, 6].

Various pathogenic factors, such as infection, tissue injury, or cardiac infarction, can induce inflammation by causing tissue damage. The etiologies of inflammation can be infectious or non-infectious (Table ​ (Table1). 1 ). In response to tissue injury, the body initiates a chemical signaling cascade that stimulates responses aimed at healing affected tissues. These signals activate leukocyte chemotaxis from the general circulation to sites of damage. These activated leukocytes produce cytokines that induce inflammatory responses [7].

Table 1

Non-infectious factorsInfectious factors
Physical: burn, frostbite, physical injury, foreign bodies, trauma, lionizing radiation
Chemical: glucose, fatty acids, toxins, alcohol, chemical irritants (including fluoride, nickel and other trace elements)
Biological: damaged cells
Psychological: excitement
Bacteria viruses other microorganisms

Suppression and resolution of allergic inflammation

Apart from the cessation of allergen-specific stimulation of effector cells, as occurs at the end of the pollen season in pollen-sensitive individuals, the factors that regulate the resolution of allergic inflammation are poorly understood. Some effector cells may undergo apoptosis as concentrations of cytokines that promote the survival of such cells locally diminish 84 others (such as mast cells) may decrease the extent to which they differentiate, mature or proliferate locally 85 and others may emigrate from the affected site 86 .

In some models of allergic contact hypersensitivity, the production of IL-10 by mast cells contributes significantly to the ability of mast cells to reduce many features of inflammation in the affected sites 87 . Whether similar anti-inflammatory or immunosuppressive actions of mast cells can be elicited in the context of IgE-associated allergic inflammation remains to be determined. However, several types of innate and adaptive immune cells that infiltrate sites of allergic inflammation (including eosinophils and various populations of regulatory T cells) can produce mediators, cytokines, chemokines and growth factors that could reduce inflammation or promote repair at these sites. Such products include the resolvin and protectin lipid mediators 88 , IL-4 (which can have anti-inflammatory effects 89 ), TGF-β 90,91 , TGF-α 92 , IL-10 (refs 16 , 87 , 89 , 91 , 93 ) and IL-35 (ref. 93).

Allergen-specific regulatory T cells have been reported in patients after allergen-specific immunotherapy 10,11,16,93 . In addition, there is evidence from animal models of allergy and asthma that both antigen-specific regulatory T cells and naturally occurring regulatory T cells can limit disease, in part by IL-10- and TGF-β-dependent mechanisms 16,93 . However, the extent to which particular populations of regulatory T cells can limit allergic inflammation at the times of exposure to specific allergen, or help to resolve allergic inflammation when exposure to allergen ceases, and the mechanisms by which the regulatory T cells exert these effects remain to be fully understood.


a localized protective response elicited by injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissue. adj., adj inflam´matory. &emsp

The inflammatory response can be provoked by physical, chemical, and biologic agents, including mechanical trauma, exposure to excessive amounts of sunlight, x-rays and radioactive materials, corrosive chemicals, extremes of heat and cold, or by infectious agents such as bacteria, viruses, and other pathogenic microorganisms. Although these infectious agents can produce inflammation, infection and inflammation are not synonymous.

The classic signs of inflammation are heat, redness, swelling, pain, and loss of function. These are manifestations of the physiologic changes that occur during the inflammatory process. The three major components of this process are (1) changes in the caliber of blood vessels and the rate of blood flow through them (hemodynamic changes) (2) increased capillary permeability and (3) leukocytic exudation.

Hemodynamic changes begin soon after injury and progress at varying rates, according to the extent of injury. They start with dilation of the arterioles and the opening of new capillaries and venular beds in the area. This causes an accelerated flow of blood, accounting for the signs of heat and redness. Next follows increased permeability of the microcirculation, which permits leakage of protein-rich fluid out of small blood vessels and into the extravascular fluid compartment, accounting for the inflammatory edema.

Leukocytic exudation occurs in the following sequence. First, the leukocytes move to the endothelial lining of the small blood vessels (margination) and line the endothelium in a tightly packed formation (pavementing). Eventually, these leukocytes move through the endothelial spaces and escape into the extravascular space (emigration). Once they are outside the blood vessels they are free to move and, by chemotaxis , are drawn to the site of injury. Accumulations of neutrophils and macrophages at the area of inflammation act to neutralize foreign particles by phagocytosis .

Chemical mediators of the inflammatory process include a variety of substances originating in the plasma and the cells of uninjured tissue, and possibly from the damaged tissue. The major kinds of mediators are (1) vasoactive amines, such as histamine and serotonin (2) plasma endopeptidases that comprise three interrelated systems, the kinin system that produces bradykinin , the complement system that produces proteins that interact with antigen--antibody complexes and mediate immunologic injury and inflammation, and the clotting system that increases vascular permeability and chemotactic activity for the leukocytes (3) prostaglandins , which can reproduce several aspects of the inflammatory process (4) neutrophil products (5) lymphocyte factors and (6) other mediators, such as slow-reacting substance of anaphylaxis and endogenous pyrogen .

Hormonal Response. Some hormones, such as cortisol , have an antiinflammatory action that limits inflammation to a local reaction while others are proinflammatory. Thus, the endocrine system has a regulatory effect on the process of inflammation so that it can be balanced and beneficial in the body's attempts to recover from injury.

Watch the video: Second Extinction Gameplay Stream October 7th 2021 (February 2023).