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Sometimes You Want Immunity Suppressed

The only evidence-based approach for “boosting immunity” is vaccination! By contrast, reducing immune function does have scientific validity, and can be very important.

“Boosting immunity” is a hot topic these days. That’s understandable since it is our immune system that protects us from invaders such as the SARS-CoV-2 virus. But boosting the immune system is a very nebulous concept because it is actually composed of a complex array of white blood cells, organs and messenger chemicals and cannot be revved up like a car engine. Poor diet, lack of exercise, stress , and lack of sleep can reduce immune activity, so remedying any of these can help “boost” the system. However, as far as the exuberantly touted vitamins, herbs, mushrooms, minerals and probiotics go, there is a lack of clinical evidence. The only evidence-based approach for “boosting immunity” is vaccination! By contrast, reducing immune function does have scientific validity, and can be very important.

Early organ transplants were plagued by rejection. The recipient’s immune system considered the organ a foreign intruder and mobilized its forces for battle. Doctors realized that if transplants were ever to be successful, the body’s immune system would have to be held in check.

By the time Dr. Christiaan Barnard performed the world’s first heart transplant in 1967, drugs that curb immune activity were available, but they left a lot to be desired. The medications managed to keep the immune system from rejecting the organ, but the extent of immune suppression was such that it left the patient susceptible to all sorts of infections. In fact, Louis Washkansky, the first recipient of a transplanted heart, died of pneumonia he contracted because of suppressed immunity. But the problem of rejection was essentially solved when cyclosporine came onto the scene in 1981.

The discovery of the first truly effective anti-rejection drug was somewhat serendipitous, and dates back to the early 1970s. In those days, pharmaceutical companies searched high and low for novel antibiotics, investigating whatever fungus they could get their hands on. After all, antibiotics isolated from fungi, such as penicillin and streptomycin, had already proven their worth. Hoping to find some novel antibiotic-producing fungus, pharmaceutical companies routinely asked their employees to bring back soil samples from their travels. The Sandoz company lucked out. A soil sample collected in Norway yielded a strain of fungus that produced a compound composed of a ring of amino acids, eventually named cyclosporine. It looked like a good candidate for antibiotic activity. Unfortunately, it turned out not to have any such property.

Eventually disappointment turned to elation when cyclosporine was found to have a marked immunosuppressive effect by decreasing the production of inflammatory cytokines by T-lymphocytes, a type of white blood cell! However, administering the drug presented a problem since it was almost completely insoluble in water. When taken orally, cyclosporine never made it into the bloodstream. But researchers discovered that dissolving the drug in olive oil did the trick. In 1978, the first kidney and bone marrow transplants in which cyclosporine successfully prevented rejection were performed in England. Today, hearts, kidneys, livers and bone marrow are routinely transplanted, thanks in large part to cyclosporine.

There is a footnote to the cyclosporine story, and a rather significant one. After a transplant, monitoring the use of all drugs taken by patients is critical because some medications can interfere with the action of cyclosporine. St. John’s wort, for example, an herbal remedy available without a prescription, can negate the effect of cyclosporine and result in rejection. This interaction came to light when a heart transplant patient’s body rejected the donated organ even though an appropriate amount of cyclosporine had been administered. Unknown to his physicians, he had been taking St. John’s wort purchased at a health food store to ward off his depression. He almost warded off his new heart.


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