Question

A 7-year-old boy with an infected wound on his leg is admitted to the emergency department. His mother states that a high fever with diarrhea occurred during the last 12 hours. Within the last 2 hours he had become very lethargic, was unable to stand, and was very disoriented. The doctor observes that his blood pressure is dangerously low and suspects that the boy is suffering from bacterial septic shock caused by the wound infection.

Discuss the role of cytokines in the pathogenesis of this disease. Speculate on future therapeutic strategies that might be employed by using monoclonal antibodies or other biologic agents to treat this disease.

Answer 1

DISCUSSION, ANSWER and EXPLANATION :

Shock is defined as a condition in which severe reduction in tissue perfusion leads first to reversible and if prolonged may result in irreversible cellular injury. The cellular injury due to inadequate delivery of oxygen and nutrients leads to production of different chemical mediators termed as cytokines that further compromise tissue perfusion.

Shock can be classified based on underlying cause:

1) Hypovolemic shock- In severe diarrhoea and vomiting or haemorrhage, big amount of fluid is lost from body leading to fall in blood pressure or shock

2) Cardiogenic shock- As in a case of big myocardial infarction, heart is unable to pump adequate blood leading to hypotension and shock

3) Anaphyactic shock - Certain drugs and insect stings produce severe instant allergic reaction causing huge amounts of cytokines released in susceptible persons,this is termed as anaphylaxis resulting fall in blood pressure is termed as anaphylactic shock

4) Septic shock- Shock due to infection by different Gram positive and Gram negative bacteria.Sepsis induced hypotension with perfusion abnormalities including lactic acidosis, oliguria (decreased urine output) and organ/tissue dysfunction.

In case of infection our immune system responds by activating leukocytes. These activated leukocytes release variety of chemical mediators (cytokines) to contain the pathogen. The released cytokines apart from killing or containing bacteria have also damaging effects on our tissue also. Important cytokines with their effects are: TNF(Tumor necrosis factor)alpha,IL-1,IL-10,IL-6 and nitric oxide are main cytokines.

1) TNF alpha is produced by macrophages. It promotes production of other cytokines. It enhances stimulation of T and B lymphocytes.

2) Interleukin- Effects of interleukins are fever, release of neutrophils from bone marrow, proliferation of B lymphocytes and and enhanced production of antibodies.

3) TNF alpha and IL-6 have cardiac depressant action thus reducing cardiac pumping activity

4) TNF alpha also induces endothelial dysfunction leading to release of nitric oxide which is a vasodilator, hence further reduces blood pressure.

Thus we can see that these cytokines start a vicious cycle in which they promote release and effect of other cytokines ultimately leading to shock.

Possible future therapies:

Monoclonal antibodies are produced by identical immune cells which react with particular antigen only.

Biological therapy means use of organism, their part or proteins for the purpose of treatment of any disease condition.

Monoclonal antibodies or biologic agents targeting cytokines or immune cells which can bind and halt further exaggeration of immune response can be a possible future therapy in case of septic shock because here, the prime culprit is exaggerated uncontrolled immune response to pathogen.Monoclonal antibodies and biologic agents can also be employed against pathogens which will identify and eliminate them like antibiotics.So,controlling cytokine release and action along with proper antibiotics to eliminate the pathogens can be a better approach to treat these conditions.