FARHAN ISHRAK AHMED
May be you are reading this while shivering under a blanket, cursing that high temperature which is making your life hell!
 Perhaps, you have already taken a couple of paracetamol pills and your mother comes momentarily with a thermometer to check how warm you are now.
But little do we know of the marvelous gift the Almighty has engineered within us and the thousands of microscopic wars that are heating up the battlefield inside our bodies.
Whatever the cause of your fever might be, let us dive into the microscopic universe of our body to see what is happening. You should give respect to that tiny little brat, a bacteria or virus, which managed to trick so many security levels. After fooling the 1st line of defense, the pathogen soon encounters the body's elite squad of fighters-the PMN cells or aggranulocytes. Neutrophils are the bravest cells which fight head on with pathogenic bacteria, alerting other members of the immune system, like a “backup call” by a police officer over a walkie-talkie.
As the gram negative bacteria is doomed, it undergoes lysis and its peptidoglycan cell wall breaks down releasing many substances, some called endotoxins. Lipopolysaccharide(LPS) is an example.
The LPS quickly binds with a protein circulating in plasma called Lipoprotein Binding protein (LBP). This LBP-LPS complex further binds with CD14 receptor of a neighboring macrophage and initiate a cascade of events, which releases cytokins, small protein molecules that are involved in cell signaling; interleukine 1 is a common example. There could also be another way, when sometimes an auto immune reaction initiates a pyrogenic reaction. Endotoxins are released by our own police force causing the same effect. Other activated immune cells come into action to backup by releasing interleukin 1 directly.
Once these pyrogens reach the brain, they cross the Blood Brain Barrier (BBB) through the circumventricular organs (CVO) where filtration is minimum and hence easy to pass into the neural tissue. There they arrive at the thermoregulatory centre, hypothallamus, where the set point for temperature is raised through the Autonomic Nervous System. This is mainly done by synthesis of Prostaglandin E2 (PGE2).
PGE2 initiates a systemic response through the autonomic nervous system (ANS) by increasing peripheral vasoconstriction, increased muscle contraction and raises the Basal Metabolic Rate (BMR) thereby minimising heatloss and increasing the body temperature above normal (37.5-38.3 C).
Why do I shiver if I am getting hot inside, you may ask?
 If the body fails to reach the new set point created by the brain, then the brain automatically causes the body to generate more heat until it is equalised. That's why you feel comfort under that warm cozy blanket. It is the increased set point in the brain which becomes higher than ambient room temperature that initiates shivering not because you are cold.
Then we might think, what's the point of warming up?
Well, most data suggests that increased body temperature enhances the activity of immune cells so that they can eliminate the threat as fast as possible. Certain enzymes which take part in phagocytosis have higher optimum temperature and chemotaxis also functions better when temperature is increased.
However, a high temperature can be fatal and lead to permanent brain damage and this is particularly true for infants. This is often the case for infants who become autistic in future following a high fever. This is why your mother cools your head down by putting a wet towel over your forehead.
Do you know how the Paracetamol tablet works?  
This wonder drug inhibits the synthesis of PGE2 you just read about earlier. This is done by inhibiting an enzyme called cyclooxygenase (COX) in the arachodonic acid pathway. In a way, this PGE2 is the culprit of your sickness.
If this enzyme is inhibited, set point is not raised so your fever cools down. But thanks to the brave soldiers inside you, the pathogen gets eliminated before it can harm you. So although it’s bitter to experience a fever, it's nonetheless a blessing from the Almighty who engineered you perfectly.                                                      
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