 One of the markers of inflammation is heat but fever is a different thing. Fever is caused by a cytokine, a specific kind of cytokine or a specific flavor of cytokine called a pyrogen, so it's caused by a pyrogen, a specific flavor of cytokine. And pyrogens are produced by damaged tissue, by usually not damaged tissue, usually a response to an invading pathogen. And so the pyrogen, this is really interesting, pyrogens enter the bloodstream. So here we go. And remember I was like, yeah, I would think that cytokines sometimes go into the blood. So here's an example. A pyrogen goes into the bloodstream. It's produced in response to an invader and it travels in the bloodstream to your thermostat zone. Where's that? Where is temperature regulated in your body? Dude, it's an integrator. It's integrated in the hypothalamus. The hypothalamus is where temperature regulation is integrated. So here comes my friend, the pyrogen. It comes into the hypothalamus and are you ready for this? It resets the set point. It pushes, pause, it redes it. What is the normal set point for temperature, body temperature? Yeah, it's 98.6 degrees Fahrenheit. So 98.6 is where incoming information from thermoreceptors in the hypothalamus says, oh, yeah, it's 98.6, this is good. If you get it up to 99.5, let's cool things down a little bit. If it gets down to 97, let's warm things up a little bit. And we have this whole system mediated by the hypothalamus. The pyrogen comes in and hypothalamus resets the set point. And now the hypothalamus says, yeah, the set point is awesome, it's 102. That's the new set point. So now, and why did it do this? Because a pyrogen, a chemical came in and messed with that area of the hypothalamus. The hypothalamus now says 102 is normal. Your temperature is below 102. You respond like you're cold. You shiver, you have the shiveries, you want to cover up in a whole bunch of blankets, and you're sweating, and it's like terrible, and you feel like hell. And then when you get up to 102, then you're like, okay, this is good, but you feel bad, your brain hurts, and you're starting to get delirious because you're not supposed to be at 102, but your hypothalamus has been reset. Now, this isn't a bad guy doing this. This is you. You initiated this process, so why? Well, there are some benefits. In fact, some of our immune cells work better. We work better. Some of our white blood cells function better. They function faster at a higher temperature. Some bacteria work worse. They are not functioning optimally at that higher temperature, so they're easier to destroy if we increase the temperature. And there was also something about ions. There was some interesting. They decrease plasma ion concentrations, and I'm not sure what the mechanism for that, like how they would go about doing that, but those changing ion concentrations in the plasma affect the bacteria or the pathogens' ability to infect you. It can be very damaging, so the cost, if you get above 106 degrees Fahrenheit, you're going to die. You might not die, but you'll have brain damage, which is not great, and it makes you feel bad. So a fever doesn't, it's not a pleasant thing, but it's a great example of, you know what, I'm going to take one for the team. I'm going to suffer through a fever. I'm going to feel like crap. I'm going to risk brain damage because if I don't, I'm going to let this bad pathogen take over my system, and I'll probably die, so it's worth it. Yeah, there's going to be some fallout for me, but it's worth doing. Another strategy that the innate immune system employs is nonspecific phagocytosis, so we're going to yumpshalize, phagocytize the bad guys, but we're going to do it in a nonspecific way because phagocytosis is also a part of the acquired immune response.