New Connections Found Between Spleen and Brain In the past, scientists discounted the importance of the spleen, a five-ounce organ located in the upper left abdomen. Now, there's an increasing understanding of the spleen's importance as a part of the immune system, filtering blood and removing old blood cells.

New Connections Found Between Spleen and Brain

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IRA FLATOW, host:

This is Talk of the Nation Science Friday, I'm Ira Flatow. A bit later in the program, AIDS vaccine research at the NIH and making experimental cancer vaccines in plants. But first, what's your spleen good for anyway? Do you know that? Do you know what happens in your spleen? There is the expression, venting your spleen at someone? But until relatively recently, the organ wasn't thought of as that important, just a reservoir for extra blood in your body. We know that it plays a role in the immune system, filtering up blood cells, old blood cells, and performing other immune tasks. But new work published this week in the proceedings of the National Academy of Sciences says that the spleen may provide a connection between the brain between your nervous system and the immune system. That nerve connections from the brain could allow one to influence the other.

Joining me now to talk about this is one of the researchers on the project, Mauricio Rosas-Ballina, he's a scientist in the Laboratory of Medical Science at the Feinstein Institute for Medical Research in Manhattan, New York. Welcome to Science Friday.

Dr. MAURICIO ROSAS-BALLINA (Scientist, Feinstein Institute for Medical Research): Thank you very much, Ira. I'm really happy to be in the program.

FLATOW: I'm happy to have you here. Let's talk about - give us an idea where the ABCs of the spleen. What it is - where does it reside? What does it do?

Dr. BALLINA: So the spleen is a - is an organ, it's a lymphoid organ that is located in the abdomen. You can find the spleen in the upper left quadrant of the abdomen. And as you've said before the spleen is - has several functions. One of them is it works as a bladder reservoir. But it is also associated with the cleaning of a certain particles. For example, red blood senescence - senescent red blood cells, and it's also involves in other immune functions that have to do with combating infections.

FLATOW: Now, what made you think and look into the idea that there could be a connection between the brain and the spleen?

Dr. BALLINA: Well, the story goes like 10 years ago, and it's not my story. It's the story of Dr. Kevin Tracey who's the head of the lab. Well he was trying to follow was a way in which these organs were communicating to the brain. And this two incidents were communicating already at the brain and the immune system. In this lab, we are trying to figure out how to deal with diseases such as sepsis. So we are trying to come with novelty approaches. In the process of trying to figure out one of these ways what people before in this lab realize that when you put strokes in the brain, in certain experimental mode of sepsis, you would find that these strokes acting in the brain would be suppressing information in the periphery. So that suggest that there would be connection between the brain, and so in some place in the, you know, in the body.

FLATOW: Mmhmm.

Dr. BALLINA: So then came experiments in which we were selecting the section in different nerves and turn out that the vagus nerve was an important part between this communication between the brain and immune system. Later on, we continue doing some more experiments, and then we found that by taking out the spleen we were reversing this protective effect that stimulating - that the stroke had. And so, that's how we come up with this connection between the brain and the spleen.

FLATOW: And it's connected by that vagus nerve?

Dr. BALLINA: That's right. Actually, the work that we're publishing - that's been published already - what it's telling is there's a connection between the brain and the spleen. So if you can imagine a map of the brain, being on the top of the map, you have the brain that is sending information through the vagus nerve which then communicates through the splenic nerve and that sends the final information to the spleen.

FLATOW: Mmhmm. And how did you actually realize the importance of this pathway? Does the brain through the vagus nerve influence directly the spleen to do something?

Dr. BALLINA: Well, the way which our most work is the following, you have a disease model, an experimental model disease. You know that it is, let's say, it's a - you know, it has - this model is associated with a certain mortality, and we have come up with the ways to stimulate the vagus nerve. So what we do is we stimulate - that actually the vagus nerve and then we see that this effect is associated with an increased survival.

FLATOW: Hmm. So by stimulating the vagus nerve the animal survives longer?

Dr. BALLINA: That's right. We can determine, and so we can proceed into experiments to figure out which is the pathway that leads to.

FLATOW: And that then is related to the immune system of the animal.

Dr. BALLINA: That's right. What we have found is that there are some cells in the spleen - the name are microphages - and these microphages are producing certain molecules which are called cytokines, specifically there's a cytokine called TNF which stands for Tumor Necrosis Factor which can be the inhibitor(ph) in certain diseases. So what we have found is that when you stimulate electrically the vagus nerve, there is a down regulation of the production of these cytokines. And that leads to improved survival.

FLATOW: So you help boost the immune system by stimulating the vagus nerve, it goes to the spleen. It says to me then that we've discovered one of these, you know the foundation possibly for the idea that our nervous system does help regulate immunity, our thoughts, things like that.

Dr. BALLINA: The health, yes. Let me try to find something, you know, our model what we are doing is actually we are turning down the production of these cytokines which we understand as cytokines that are actually producing a harm by increasing inflammation in your body. So by stimulating the nerve, we are kind of dampening that response. But you're right, I mean, we are basically modulating the immune system by modifying or intervening in the nervous system.

FLATOW: So what other kinds of diseases then besides sepsis that you studied might be influenced?

Dr. BALLINA: Well, I mean up to now there are like - we have several modes of disease. For example we have found that by following these techniques, you can improve survival in - for example hemorrhagic shock. You can also find improved survival in the modes of pancreatitis and I mean, the options are out there. And let's see if we can include more disease into the list.

FLATOW: Hmm. I have a question here from Second Life. Lore (ph) says, so you're in - say your digestion may be connected with your immune system? I guess that's the question.

Dr. BALLINA: Yes. I mean, you know, the brain is governing several functions in your body. You have not only networks that go from the brain to the periphery but you also have afferent(ph), very sensitive fibers that are collecting information from the periphery to the brain. So, yeah, there may be a way in which we - I mean for the digestion, information comes from digestion is coming to the brain. And then, this information is coming down to the immune system to modify it.

FLATOW: Hmm. Let's go to the phones. David in Aspen. Hi, welcome to Science Friday.

DAVID (Caller): Hi, Ira.

FLATOW: Hi there.

DAVID: I'm a survivor of a hematological cancer. And at one point during my treatments, my doctor recommended a splenectomy.

FLATOW: Removal of your spleen.

DAVID: Correct.

FLATOW: Yeah.

DAVID: Because of increased platelets.

FLATOW: Hmm.

DAVID: Wondering, since I chose not to proceed with that, how that might affect, how might it have affected my immune system?

FLATOW: All right, Dave, thanks.

Dr. BALLINA: Well, the answer to the question is it's difficult to answer. There's obviously a very well-documented increase in susceptibility to infections, specifically to infections to streptococcus pneumonia, if you don't have a spleen. Based on this discovery of the spleen and the brain communicating with each other, we really haven't figured out what's the implications of not having a spleen in terms of this communication between the brain and the spleen. So it's difficult to answer that question in terms of if your brain is going to still going to be able to work properly to modify immune functions that happen in the spleen.

FLATOW: What kinds of things going on in your brain affect the vagus nerve? I mean - this - would - you know, I'm trying to think of if you do yoga, if you do tai chi or some sort of thing, does that work to your vagus nerve and stimulate it?

Dr. BALLINA: Yeah, that's right. Actually, there are some stories that make association between different types of mental states or therapies that includes like biofeedback. These stories - what that they found is that there is a connection between - that there is an increase in vagus nerve activity while you perform these activities. And on the other hand, we also have found that there are some inflammatory diseases that are associated with a decreased activity of the vagus nerve. So, this kind of suggests that if you can, somehow, with these kind of exercises, by feedback, you can increase the activity of the vagus nerve, you can probably hopefully modify in some way your immune system.

FLATOW: Now, are there any nutrients you can take that would increase this activity of your spleen or the vagus nerve?

Dr. BALLINA: Well, not that I know, at this moment. There are some drugs that we are trying to develop that to try to target several aspects of this pathway, and we are trying to figure out if these drugs either as a compound, you know, that you can get in some medicines, or through natural nutrients can somehow act on cells of the immune system in which the pathways working to modify and modulate any responses.

FLATOW: Mm-hm. And what is your next step now? Where would you like to take - to take your research next?

Dr. BALLINA: Well, one part that's really interesting is that the spleen is a place where you have several types of immune cells. You have macrophages, as I have said before.

FLATOW: Those are white blood cells?

Dr. BALLINA: These are white blood cells. Yes, white blood cells can be divided in macrophages, monocytes, and lymphocytes. But there are only some types in the spleen. We can probably try to modify other immune functions that are associated with those cell types, for example, antibody production and probably in relation to the response of other infectious diseases.

FLATOW: This would also argue that if, you know, we hear so many people who have car accidents or whatever and they've had their spleens removed for injury. Would it not argue that surgeons should try to save the spleen now as much as they can rather than get - than remove it?

Dr. BALLINA: Well, I mean, the indications for removing the spleen are very clear and there are some situations to which it is necessary to do it or otherwise you have huge hemorrhaging. and it's going to be ending up very badly. The fact that we have discovered this pathway would probably kind of probably go back and try to study what's happening with these patients that don't have a spleen. And in terms of their modification of their immune system by the nervous system and if there's a change in that that can be, you know, prevented by not doing the spleen then there's going to be some serious work to be done to determine what's best to do.

FLATOW: And I guess they should - there would be more research that we'd like to see into what other kinds of mental processes use - affect the vagus nerve.

Dr. BALLINA: Yeah. Definitely, yes. I think that, for example, it's interesting to know if, you know, depressive states are modifying how your immune system is working through this badly(ph), for example.

FLATOW: Do you know that research is going on in that field at all?

Dr. BALLINA: At least not in our group. I know some other groups that are starting to do these kinds of questions and soon, I hopefully will have answers.

FLATOW: And you're going to go from here to do, what? Next step for you?

Dr. BALLINA: Well, you mean I might, and so I am - we're trying to figure out the exact mechanism in the spleen. So, where we're reducing our scope of study to the spleen and we have - and probably try to figure out the exact mechanism by which, you know, neurotransmitters released by nerves in the spleen are affecting cells in the spleen.

FLATOW: Well, good luck to you.

Dr. BALLINA: Thank you very much, sir.

FLATOW: And thank you for taking time to be with us today.

Dr. BALLINA: My pleasure.

FLATOW: Dr. Mauricio Rosas-Ballina, a scientist in the laboratory of medical science at the Feintein Institute for Medical Research. That's in Manhasset, Long Island. We're going to take a break and then come back, change gears, talk with Dr. Anthony Fauci, is going to be here talking about the future for an AIDS vaccine. What direction should the research go in? And why was a research trial canceled? We'll get into all of that. Take your calls, 1-800-989-8255. Stay with us, also in Second Life. We'll be right back after the short break.

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