Cytokine release syndrome
Encyclopedia
Cytokine release syndrome is a common immediate complication occurring with the use of anti-T cell
antibody
infusions such as ATG
, OKT3
and TGN1412
. Severe cases are known as cytokine storm
s.
The pathogenesis is that the antibodies
bind to the T cell
receptor, activating the T cells before they are destroyed. The cytokine
s released by the activated T cells produce a type of systemic inflammatory response
similar to that found in severe infection
characterised by hypotension
, pyrexia and rigors
. The patient feels very unwell, as if in a high fever
– indeed, the cytokine release syndrome is effectively a type of non-infective fever.
Deaths due to cytokine release syndrome with OKT3 (muromonab-CD3) have been reported, and it can cause life-threatening pulmonary edema
if the patient is fluid overloaded. However, if treated appropriately it is usually not dangerous, just extremely unpleasant for the patient.
The effect is greatly reduced by using low dose OKT3 e.g. 2 mg instead of 5 mg, slow infusion instead of rapid injection, intravenous administration of an anti-histamine (such as chlorphenamine
) and a corticosteroid
(such as hydrocortisone) prior to starting the ATG/OKT3 infusion, with further doses of anti-histamine and steroid given during the infusion if necessary, Acetaminophine 500 mg by mouth 1 hour before infusion to prevent fever. Moreover, it is recommended that any overhydration to be corrected before the administration the 1st dose either by dialysis or with intravenous furosemide, to prevent the possible development of pulmonary oedema.
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
infusions such as ATG
Anti-thymocyte globulin
Anti-thymocyte globulin is an infusion of horse or rabbit-derived antibodies against human T cells which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia.-Uses:...
, OKT3
OKT3
Muromonab-CD3 is an immunosuppressant drug given to reduce acute rejection in patients with organ transplants. It is a monoclonal antibody targeted at the CD3 receptor, a membrane protein on the surface of T cells...
and TGN1412
TGN1412
TGN1412 is the working name of an immunomodulatory drug which was withdrawn from development after inducing severe inflammatory reactions in the first human subjects to receive the drug....
. Severe cases are known as cytokine storm
Cytokine storm
A cytokine storm, or hypercytokinemia is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.-Symptoms:...
s.
The pathogenesis is that the antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
bind to the T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
receptor, activating the T cells before they are destroyed. The cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s released by the activated T cells produce a type of systemic inflammatory response
Systemic inflammatory response syndrome
Systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently a response of the immune system to infection, but not necessarily so...
similar to that found in severe infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
characterised by hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, pyrexia and rigors
Rigor (medicine)
Rigor is a shaking occurring during a high fever. It occurs because cytokines and prostaglandins are released as part of an immune response and increase the set point for body temperature in the hypothalamus....
. The patient feels very unwell, as if in a high fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
– indeed, the cytokine release syndrome is effectively a type of non-infective fever.
Deaths due to cytokine release syndrome with OKT3 (muromonab-CD3) have been reported, and it can cause life-threatening pulmonary edema
Pulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
if the patient is fluid overloaded. However, if treated appropriately it is usually not dangerous, just extremely unpleasant for the patient.
The effect is greatly reduced by using low dose OKT3 e.g. 2 mg instead of 5 mg, slow infusion instead of rapid injection, intravenous administration of an anti-histamine (such as chlorphenamine
Chlorphenamine
Chlorphenamine or chlorpheniramine , commonly marketed in the form of chlorpheniramine maleate , is a first-generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. Its sedative effects are relatively weak compared to other...
) and a corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
(such as hydrocortisone) prior to starting the ATG/OKT3 infusion, with further doses of anti-histamine and steroid given during the infusion if necessary, Acetaminophine 500 mg by mouth 1 hour before infusion to prevent fever. Moreover, it is recommended that any overhydration to be corrected before the administration the 1st dose either by dialysis or with intravenous furosemide, to prevent the possible development of pulmonary oedema.
See also
- cytokine stormCytokine stormA cytokine storm, or hypercytokinemia is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.-Symptoms:...
, life threatening massive release of cytokines