This is in follow-up to our class discussion of how immunosuppression can be classically conditioned. We discussed a study in which cyclosporin (an immunosuppressive drug) was given to rats along with a sweet-tasting drink. After multiple pairings, just the sweet-tasting drink was given and it was observed that the rats had the same immunosuppressive response WITHOUT the cyclosporin! This is fascinating because it means that the immune system can actually learn to associate environmental cues with a response.
Another study (Goebel, et al, 2002) found this same effect in humans. After pairing cyclosporin with a novel-tasting drink four times, just the novel-tasting drink produced the same immunosuppressive effects. These effects included reduced IL-2 and IFN-y mRNA expression in peripheral blood lymphocytes, and less secretion of IL-2 and IFN-y by CD3+CD4+ (Th) lymphocytes.
An antihistamine effect has also been conditioned in humans (Goebel, et al, 2008). Patients with allergic rhinitis were given the anti-histamine desloratadine along with a novel-tasting drink once daily for 5 consecutive days. Nine days later, some were re-exposed to the novel-tasting drink along with a placebo pill, some were given water with a placebo pill, and some were given water and the desloratadine. The water-plus-placebo group showed reduction in subjective total symptom scores and histamine skin prick test results, but no basophil inhibition (did the placebo pill act as a weaker-acting conditioned stimulus?). The group who received the novel-tasting drink with a placebo pill showed reduction in subjective total symptom scores, reduction in skin prick reactions to histamine, and basophil inactivation in degrees that were similar to the group who received the desloratadine and water.
What about immune system activation? Studies show that it can also be classically conditioned! In one such study (Pacheco-Lopez, G. et al, 2004), researchers injected the superantigen staphylococcal enterotoxin B (SEB) into rats while giving them a saccharine-flavored drink. One week later, presenting just the drink induced a strong taste aversion response and increased plasma levels of corticosteroid, INF-y, and IL-2.
What does this mean? It means that strong signals associated with immune-acting drugs are noticed by the immune system. After multiple exposures, the effect of a drug on the immune system is not only due to specific drug mechanisms anymore, but includes the effects of learned responses. So, there must be some link between the CNS gustatory system and the immune response. There are so many questions about how this actually occurs, making it a totally exciting field for more research!
Goebel, M., et al (2008). Behavioral conditioning of antihistamine effects in patients with allergic rhinitis. Psychotherapy and Psychosomatics,77(4), 227-34. http://proquest.umi.com/pqdweb?index=0&did=1479529181&SrchMode=1&sid=1&Fmt=6&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1324060097&clientId=18952
http://www.ncbi.nlm.nih.gov/pubmed/18418029
Goebel, M., et al (2002). Behavioral conditioning of immunosuppression is possible in humans. The FASEB Journal, 16, 1869-1873. http://www.fasebj.org/content/16/14/1869.full
Pacheco-Lopez, G. et al (2004). Behavioural endocrine immune-conditioned response is induced by taste and superantigen pairing. Neuroscience, 129, 555–562. http://www.sciencedirect.com/science?_ob=MiamiImageURL&_cid=271071&_user=418620&_pii=S0306452204007742&_check=y&_coverDate=2004-01-01&view=c&wchp=dGLbVBA-zSkzS&md5=206c181608005e8a34afe66bf9cb7a8c/1-s2.0-S0306452204007742-main.pdf
This idea of conditioned immune responses is really interesting. I wonder if this expands into other types of drugs and whether patients have unintentionally experienced this: for example if they always have a glass of orange juice with their drug and once their treatment regimen is done they drink orange juice, do they feel like they are still on their drug?
ReplyDeleteI think MerryL7630 has a point. For years chicken soup made me feel vaguely ill, since it was always served to me when I actually WAS ill. I thought it was just in my head, but now I'm sure there were real physiologic reactions going on.
ReplyDeleteRobert Ader, one of the founders of the study of brain, behavior, and immunity, and the author of the experiments on conditioned immunosuppression in lupus mice, died yesterday (20 December). An obituary describes his contributions:
ReplyDeletehttp://www.urmc.rochester.edu/news/story/index.cfm?id=3370
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