Does anybody know how I can induce immune suppression in normal laboratory animals (rodents) without using drugs. Needless to say I cannot use nude or SCID mice. On the other hand, I do not want to use immunosuppressive drugs. Thanks in advance.
Hi! You can try to keep them in the unnormal conditions, like too cold or too hot temperature, lower or higher humidity etc. But it will be difficult to measure effect. Why not drugs?
Over-exercise induce immune suppression in humans. Cannot give you info for rodents, but would expect it to be similar.
You haven't said whether you are trying to create a defect in innate or adaptive immunity or both, and why you want to do this in the first place. As such it's difficult to give more than a general answer.
Your options are also limited without resorting to drugs. You can sublethally irradiate the mice (selectively killing T and B cells) giving you a transient defect in adaptive immunity, or you could perform a thymectomy to eliminate mature T cells. In both cases it is going to be difficult to titrate the effect (both are all-or-none) unlike with drugs. Why are drugs not an option?
Chronic stress. Choose the most appropriate stressor(s) for your settings (one or combination) physical and/or 'psycho-emotional'. For example, 1 - suggested above forced 'over-exercise' which can be easily achieved by swimming. Good thing about it you can measure and dose it; 2 -- over-crowding (just one or two extra animals per cage); 3 -- irregular rehousing; 4 -- irregular circadian changes; 5 -- exposure to the predator (e.g. rat for mice); 6 -- water in the cage (not much, just to make it wet). Depending on what you consider immunosuppressive drugs -- you might want to consider low doses of corticosteroids.
Hi- what kind of immunosuppression are you trying to achieve? Specific type of cells? (i.e. T-cells?) . Can you use dietary supplements? The active form of vitamin D- calcitriol is very potent at suppressing immune responses, especially Th1 and Th17 cells. Can give calcitriol orally (usually with gavage) or inject via IP. UV radiation, as suggested above by Vijaykumar Patra will also work to suppress T-cells.
Dear All!
Thank you very much for your valuable challenging answers. As I want to simulate the space environment in my experiments, I don't want to use SCID mice or any immunosuppressive drugs. Please note that immunosuppression in space is a major problem that limits the duration of human stay in space. According to NASA "Immunosuppression in space was first observed in astronauts of the Apollo and Skylab missions. More than half of the Apollo astronauts experienced infections during, immediately after, or within one week following spaceflight".
Again thanks.
Maybe this reference could help you
Neuroimmunomodulation. 2005;12(3):173-81.
Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading.
Aviles H1, Belay T, Vance M, Sonnenfeld G.
Space flight is a complex stress environment, so if you want to model it in your lab you might want to combine as many stressors as you can/want. Obviously, you can’t create microgravity but you can create almost all other ones including fluid shift by the tail-suspension (well established model). It is next to impossible to combine some of the stressors together, but perhaps it is not necessary. Or, by the way, you will probably have difficulties to make animals do it willingly as astronauts and cosmonauts do. You might have problem with the subjects’ motivation unless you have access to LOOOOTS of cheese. On the other side, similar immune suppression is observed in other ‘stressed’ categories: deep-see divers, widow(er)s, caretakers of terminally ill and/or bed-bound relatives, etc. So as you can see, the immune suppression you have mentioned, is not spaceflight –specific. It is more stress-induced. If you will search ‘stress vs immune suppression’ or ‘neuro-endocrine-immune’ you will find a lot of the literature with the mechanisms: role of ‘stress-hormones’ cortisol, catecholamines, opioids, herpes virus reactivation and many more. Good luck! And one another thing: when you will start your study it is helpful to say “POEKHALI!!!”. That is what Yury Gagarin said in 1961 right before the liftoff.
Thank you very much for your comment. I'll try "Poekhali" if it helps!. Could you please send me a reprint of your paper "Immune System Dysregulation Occurs During Short Duration Spaceflight On Board the Space Shuttle".
Since this is space flight induced, gamma irradiation would seem the most logical. I do not believe space craft are led lined. If it is a stress related combination effect you want then thoracic duct cannulation will do the trick.
May be simplest and cheapest way is usage of regular chilling/hibernation of the animals.
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