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This is a very important question, which I'll try to answer as clearly as possible. First, a word of warning: This doesn't look like the appropriate kind of article to be posted on HN. As a doctor, it's hard to understand all that's going on, and even harder to appreciate what the real impact of this research is. Laymen should completely ignore this kind of articles, and read instead clinical trials or meta-analysis that report practical outcomes people are actually interested in, like life expectancy, cure rates, exercise capacity, weight loss, etc. This paper is about some molecular mumbo-jumbo that is not very interesting in itself, unless you're a researcher in the area. Now, to answer the question. Classically, inflammation was defined by Celsus and Galen as 5 cardinal signs (in latin): - Tumor (swelling)
- Calor (warmth)
- Rubor (redness - more noticeable in light skin; don't forget that Celsus and Galen worked primarily with patients from Europe and the Middle East)
- Dolor (pain)
- Functio laesa (loss of function) These are clinical signs, that is, something the doctor can observe at the bedside. Think of when you fall and hurt your knee: the area where the impact happens swells. It might become warm to the touch. The skin might become red (different from bleeding). You'll feel pain, and for a while, your knee won't work very well because it hurts (loss of function). You don't need any fancy equipment to analyse these signs. Now, these are adaptations of the body to injury: redness and warmth appear because the blood vessels in the skin dilate in response to injury. Blood brings red blood cells, which caus redness, and heat from the inside of the body, which causes the skin to be warm to the touch. The blood vessels also "open holes", which causes the liquid part of the blood to escape the bloo vessels and get between the cells, thus causing swelling. The injured cells release signalling substances, which are detected by neurons in the skin, thus causing the individual to feel pain. Finally, some or all of these changes, might cause the limb to lose it's usefullness (because it hurts and it's swollen). The goal of inflammation is to bring white blood cells to the place of the injury in order to fight a possible infection and assist in the repair of the injured tissue. Pain doesn't help protect or repair the tissue directly, but it notifies the organism to the fact that something wrong is happening, which causes the brain to act appropriately: remove the limb from a hot surface in the case of a burn, protect a wound, etc. People that are not sensitive to pain have serious problems from childhood because they lack these indirect protective responses (they won't remove their hand from burning coals, even as they smell their flesh burning, for example) This is the classical picture of inflammation, caused by a wound or trauma to the body. It's simple, and it's functions are (nowadays) obvious. But we can go deeper... Let's talk about pneumonia. Pneumonia happens when a bacteria or virus overwhelms the defenses of the lungs, and starts reproducing in the normally microorganism-free lung. This causes blood vessesls to upen up (thus causing swelling), to dilate (thus causing redness), but the lung probably doesn't get any warmer - it's already pretty warm. The patient will not feel pain. After all, the inside of the lung doesn't have nerves capable of feeling pain! (the outside does, and if the inflammation gets near the peripheral part of the lung, it might be VERY painful). Maybe the lung won't get any warmer (it's already pretty warm already). You will run a fever, but that's not the same kind of warmth we've discussed. You will feel breathlessnes, that is, loss of function of the lung. So, while some things are common the picture gets murky. Also, the body is working very hard to defend itself, and is now producing lots of molecules that circulate in the blood and which we associate with "inflammation". We now need some fancy equipement to detect these molecules: our 5 senses are not good enough. Even though the swelling if the lungs can be detected by auscultation (with a stethoscope), the doctor probably use somethin like an X-Ray machine to visualize the swelling. Let's go deeper. Some bacteria enter the bloodstreem and latch to a valve of the heart. This kind of infection is called an endocarditis. The valve has no blood vessels, so you won't get swelling. You won't get redness or warmth either (again, you ill run a fever, but that's different). The valve also has no nerve endings, so you will feel no pain! The bacteria will happily eat your valve away (and when it's eaten away you'll die), but it may take time, and meanwhile, the valve can work relatively well. So, no loss of function. Yet, your body is fighting in overdrive to clear the infection and kill the bacteria. In fact, lots of mollecules associated with inflammation are running wild all through the body, sometimes causing as much damage as the infection itself! These are the same mollecules your body produces in pneumonia, and also in other kinds of "deep" infections. So, in a sense, even though we have amost none of the 5 classical signs of inflammation, we have a response of the body that aims to defend it against infection. So we might decide to call it inflammation. Again, we can't see the inflammation here. We need some fancy machines to see the damaged valve (even though we can listen to the valve failing with a stethoscope), and fancy lab equipment to detect these molecules, as well as the consequences of the inflammation inside the body. If we go even deeper, we'll "discover" that heart attacks (technically "myocardial infarctions") are the result of inflammation too. Even though what the patient feels is just pain, possibly followed by loss of function: breathlessness and death. So, at each step, we get further removed from the intuitive description of inflammation, which you can feel with your hands and see with your eyes, into a scary realm only accessible with the help of lab equipement and thick books. At this point, inflammation is actually a buzzword that means little... This paper's conclusion doesn't mean that the hypothalamus (a part of the brain) is red, swollen, warm, painful or has stopped functioning. That would be an encephalitis, an extremely serious disease that will land you in a hospital or a coffin (see the movie "Contagion" for some realistic depictions of encephalitis). It means that some cells, vaguely associated with inflammation, are producing some mollecules which in most parts of the body are associated with inflammation. In most situations, inflammation is either bad or signals something bad. In this situation it certainly seems bad: the concrete changes that inflammation brings to the brain seems to be similar to the ones caused by diabetes (according to my cursory reading of the article). But I agree that the word has been used for so many things, that you can't actually tell whether inflammation is good or bad. On the other hand, inflammation is a defense mechanism of the body. So what is a person with no inflammation at all? It's a person really close to death, because Nature is scary and full of bugs, and someone incapable to mount an inflammatory response is what bacteria, viruses and fungi call dinner. People like these exist (either from birth or due to unfortunate circumstances), and we can only keep them alive by keeping them in very clean rooms and pumping them full of antibiotics until their immune system (and the capability to mount an inflammtory response) recovers. Using the same word for what protects us from infection and for what turns our brains into something similar to the brains of a person with untreated diabetes is confusing. We're at a point where when a doctor talks about inflammation, it has a dompletely different thing in mind from laymen. A doctor might even have something completely ifferent in mind from another doctor or from a researcher (which is more serious). In the end, I have nothing to tell you except that you're right to be confused, and if it serves as a consolation, I'm often similarly confused when I read the titles of these papers (and sometimes the abstracts), even though I've been studying these things for years. |
Let me confidently assure you that inflammation in the hypothalamus is a dominant feature of obesity, and obesity is currently one of the top diagnosed medical problems in America. This stuff isn't hypothetical, but well accepted within the clinical research field for metabolic disorders.
Please don't recommend laymen avoid reading articles like this. That's rather senseless. While this stuff hasn't become standard in medical school curricula yet, it definitely will be some day, particularly when we are more confident in interventions that prevent hypothalamic gliosis.
EDIT: also, don't discount hypothalamic inflammation based on what you know about encephalitis. Some parts of the hypothalamus (the arcuate nucleus, in particular) are highly susceptible to inflammation because they are surrounded by a characteristically porous part of the blood brain barrier (behind the hypophyseal portal system). This allows bulky blood-born protein hormones (like leptin and insulin) to make it into the sensory neurons.
Indeed this part of the brain doesn't become red and painful, but something more relevant happens. Microglia surround the neurons responsible for appetite suppression and kill them off, which permanently changes the body fat setpoint that the brain strongly defends. There is definitely a profound and sometimes irreversible loss of function here, and that's the current focus in research. Hopefully some day we will find ways to drive repair of these circuits.