The discovery of cyclosporine was purely accidental, and the story begins with a handful of loamy soil from a Norwegian plateau called Hardanger. A researcher passing through this place took a small bag of soil from this barren land by hand due to his professional habits. Little did he know that it was this humble soil that would lead to a glorious saga in the history of medicine. Researchers isolated a new fungus from this soil and extracted compounds from these fungi, which are the cyclosporine we use now, so cyclosporine was originally called cyclosporine or cyclosporine, and then people gradually simplified it to cyclosporine. But this drug development is not a smooth sailing. We all know that penicillin, streptomycin and so on these antibiotics are originally manufactured by mold, we human beings only the mold manufacturing products isolated processing, packaging finished products. Therefore, at the beginning of the separation of the manufacture of cyclosporine was intended to use it as an antibiotic to treat diseases caused by bacteria, fungi and other infections, but the experimental results were disappointing. It was later demonstrated that cyclosporine had a very powerful immunosuppressive effect with minimal side effects that did not affect liver function, kidney function, or ovarian function. This was a very big step forward at that time because most of the immunosuppressive drugs such as cyclophosphamide, azathioprine and hormones at that time, although cheap, were not very effective and had a lot of toxic side effects. This drug was first widely used in organ transplantation and bone marrow transplantation patients, and it can be said that the application of cyclosporine was a milestone in organ transplantation. Why do you say so? Because when you do an organ transplant, you have to transplant someone else’s organ into the diseased body, and generally, a reaction that is bad for the patient, called rejection, occurs. A rejection reaction can destroy the function of the transplanted organ or even endanger the patient’s life if it is severe. The cause of graft rejection is the abnormally activated immune system in our body. Since rejection is a very strong immune response, some other immunosuppressants are very difficult to control the rejection reaction, while cyclosporine can suppress the rejection reaction very well. In the 1970s and 1980s, it can be said that thousands of patients’ lives were saved due to the clinical application of cyclosporine in organ transplantation. The success of its application in transplant patients led many rheumatologists to think that cyclosporine should have a better therapeutic effect on many rheumatologic diseases, and this was found to be true after research. It has been found that cyclosporine has good therapeutic effect on rheumatoid arthritis, lupus erythematosus and other rheumatic immune diseases, and these findings have stirred up the medical and pharmacological circles. Experiments have proven that animals using cyclosporine survive more than 10 times longer than those using conventional drugs such as azathioprine and hormones. Now cyclosporine is commonly used as an immunosuppressant in rheumatology and organ transplantation departments. The eventual acceptance of cyclosporine and its emergence as a rising star among immunosuppressive drugs is related to its compelling effects and irreplaceable advantages, as it has a powerful immunosuppressive effect and less toxic side effects than other general immunosuppressive drugs. We know that rheumatic immune disease is an abnormal activation of the immune system. When our immune system is activated, there is a characteristic that many cells of the immune system grow rapidly, not only the size of the cells will grow, but also one cell will quickly become many similar cells, which is called cell proliferation in medical science. The rapid proliferation of immune cells is a very important part of the immune response, so it has become the dream of many rheumatologists to control the rapid growth of immune cells. Most of the immunosuppressants developed for this reason perform immunosuppressive functions by inhibiting the excessive proliferation of immune cells. However, general immunosuppressants not only inhibit the proliferation of immune cells in the body, but also inhibit the proliferation of other normal cells in the body as well. There are many cells in our body that have proliferative properties under normal circumstances, such as bone marrow cells, ovarian cells, gastrointestinal cells, etc. If the normal proliferation of these cells is inhibited, it will lead to a series of side effects. General immunosuppressants may have the following side effects, such as inhibiting the growth of white blood cells, reducing white blood cells and risk of infection; reducing red blood cells and hemoglobin, reducing the body’s oxygen transport capacity and resistance; inhibiting germ cell metabolism, affecting fertility and fetal development, leading to fetal malformations, etc. Cyclosporine does not have these side effects. Cyclosporine, on the other hand, does not have these side effects. So why does cyclosporine have fewer side effects than other immunosuppressants? This has to be explained by its mechanism of action. Among the immune cells, there is one type of cell that is very critical, and this type of immune cell is medically known as T cells. When the immune system is abnormally activated, T cells grow very fast, and in a week’s time, one T cell can divide into thousands of cells, and for T cells to grow quickly, they need a very important thing, interleukin-2 (IL-2). This IL-2 is like a stimulant for T cells, only with IL-2, T cells proliferate quickly and produce a lot of T cells, while without IL-2, T cells are like asleep and don’t proliferate. Cyclosporine inhibits the proliferation of T cells precisely by suppressing the production of IL-2 in the cells. Since IL-2 has no excitatory effect on other cells in the body, cyclosporine can suppress the immune response caused by T cells by inhibiting their proliferation with high selectivity. By analogy, if a general immunosuppressant is a “cannonball”, cyclosporine may be a “laser-guided bomb”. We know that when you shoot a cannon, you can destroy the enemy, but because it is not so accurate, it may hurt civilians or buildings. Cyclosporine, as a “laser-guided bomb”, is able to strike and control the current situation more precisely without affecting the normal work of the cells and the normal functioning of the human body, so the side effects are relatively small. Some patients must have questions, then why is there a large list of side effects in the manual? The fact that the side effects are relatively small does not mean that there are none. The main side effects of cyclosporine are as follows: 1. Nephrotoxicity, which is also the main side effect of cyclosporine. However, this functional nephrotoxicity usually does not cause permanent kidney damage and can be recovered after dose reduction or discontinuation. Moreover, cyclosporine chronic nephrotoxicity is closely related to the susceptibility of individuals, which means that not everyone who uses it will develop nephrotoxicity, and it varies from person to person. Therefore, close monitoring of creatinine, urea nitrogen and other kidney function related indexes should be done before and during the use of the drug to adjust the drug in time. This is also the reason why after using the drug, doctors repeatedly emphasize that they must regularly follow up and regularly check the blood routine, liver and kidney functions. 2. Hypertension: Some patients can develop hypertension after cyclosporine treatment. The incidence is similar in adults and children, and most of the hypertension caused by cyclosporine treatment can be controlled by drugs. Elderly patients in particular need to pay attention, and patients who also suffer from hypertension should use this drug with caution. Therefore, patients with hypertension need to inform your doctor so that he can fully understand your physical condition in order to better use the drug safely. 3. Like other immunosuppressants, cyclosporine can increase the risk of lymphoma and other malignant tumors, especially skin cancer. And for lymphoproliferative diseases, it is effective to stop the drug immediately when it is found. Considering the potential risk of malignant skin lesions, affected patients taking cyclosporine treatment should avoid excessive exposure to ultraviolet light. 4. There are other side effects such as malignancy, hirsutism, gum enlargement, gastrointestinal disorders, abnormal sensation, tremor or headache, but these side effects can usually disappear after reducing the dosage or stopping cyclosporine. Other things to be aware of are that the effectiveness of vaccination may be reduced during treatment with cyclosporine and live attenuated vaccines should be avoided. One characteristic of cyclosporine is that it varies greatly from individual to individual. Some people take 2 capsules to be effective, while others may need to take 6-8 capsules to be effective. Why is this? It is mainly due to the different absorption and metabolism of each person. Therefore, we need to frequently draw blood to check the concentration of cyclosporine in the blood, and adjust the medication plan according to the blood concentration, and it is recommended that we should frequently check the blood concentration of cyclosporine and not be afraid of trouble. Otherwise, either too much may be taken to cause excessive immunosuppression or toxic side effects, or the amount used may not be enough to achieve the therapeutic effect. If you have hepatitis or poor liver or kidney function, you should check more frequently. All immunosuppressants are a double-edged sword, good use is beneficial to the treatment of disease and can effectively control the occurrence of toxic side effects; bad use, inexperienced doctors or patients on their own indiscriminate use of drugs, it is possible that the disease is not cured, but the emergence of infection or side effects. Therefore, it is recommended that cyclosporine should be prescribed by a doctor experienced in immunosuppressive treatment, and that the patient should come back for regular follow-up. This is the only way to achieve safe use of the drug and effective treatment.