Study On Methamphetamine And Morphine Regulating The Th1/Th2 Cytokines Expressions

Immune balance is important for maintaining normal functions of the body immunity.T lymphocytes play an important role in maintaining the process of immune system balance.According to helper T cells(helper T cells,Th)producing different cytokines,Th can be divided into two functional subsets:Thl and Th2.Abnormal function or imbalance of Th1/Th2 cell is the root of many autoimmune diseases.The roles of Thl and Th2 were different in immune regulation because of its secreting different cytokines.The cytokines of Thl and Th2 antagonize each other,it is help for subpopulation differentiation and immune balance.Th1 cells secrete y-interferon(IFN-y),interleukin-2(IL-2),tumor necrosis factor-β(TNF-β)and interleukin-12(IL-12)and so on.It can mediate cell immunity,which activaties macrophages,kills the parasite within cells,induces delayed-type hypersensitivity.Its major transcription factors include T cell surface expression of the T-box(T-box expressed in T cells,T-bet)and signal transduction promoter and activator of transcription 4(signal transducer and activators of transcription 4,STAT4).However Th2 mainly produces interleukin-4(IL-4),interleukin-5(IL-5),interleukin-10(IL-10)and interleukin-13(IL-13),is involved in B cell maturation and mediates humoral immunity.GATA-binding protein 3(GATA-binding protein-3,GATA3)and signal transducer and activator of transcription 4(signal transducer and activators of transcription 6,STAT6)were the main transcription factors of Th2.Methamphetamine(Methamphetamine,METH)belongs to amphetamine-type stimulants(amphetamine-type stimulants,ATS),is also known as deoxygen ephedrine.It has many pharmacological and toxicological properties,such as drug addiction(mainly psychological dependence),central nervous system stimulant role,hallucinogenic action,appetite suppression and sympathomimetic effects.In recent years,METH as the representative ATS overflow rapidly in the international area.ATS induces dysfunctions of cellular and humoral immunity of the body,weakenes body resistance,leads to susceptibility to Human Immunodeficiency Virus(HIV)and other viruses.It can cause the immune system disorder,enhance the replication of retroviruses,thereby increases viral resistance,weakens the effect of treatment of disease.Morphine(morphine,MOR)is an opioid receptor agonist,is a five rings molecule with benzyl quinoline Lin in the core.It can inhibit cough,release pain,stop diarrhea,regulate hypnotic regression and induce euphoria,finally leads to addiction.Morphine and other opioids may induce direct or indirect effects on the immune system through the central nervous system,and destroy the immune function.Thioredoxin-1(thioredoxin-1,Trx-1),is also known as interleukin-1-like cytokines,adult T-cell leukemia-derived factor,early pregnancy factor.It is a multifunctional protein that widely exist in eukaryotes and prokaryotes.Addition to the basic function,redox regulation of Trx-1,it is also involved in various physiological processes,such as the anti-oxidative,the inhibition of apoptosis,regulation of transcription factor activity.In addition,Trx-1 is also related to many human diseases:such as cancer,acquired immunodeficiency syndrome,autoimmune disease and so on.Thus,its relationship with human diseases attracts the attention of people.In this study,we used administration of METH or MOR on mice and Trx-1 oevrexpression transgenic mice to make addiction model.We explored the effects of METH and MOR on the immune balance and the roles of Trx-1 in the regulating effects of METH and MOR on the immune balance in mice spleen.The results showed that METH addiction significantly reduced the expressions of GATA3,STAT6,IL-10,which were the Th2-associated factors.And the expressions of the Thl-associated factor:STAT4,IL-2,IFN-γ were significantly increased,indicating that METH addiction cause the Th1 cell migration balance,while in mice overexpression of Trx-1 this shift was relieved.We also found that the addiction of MOR can induce Th2-associated factor such as GATA3,STAT6 and IL-10 were upregulated,while the Thl-associated factor,T-bet,STAT4,IL-2 and IFN-y were decreased,indicating morphine addiction induced immune balance to Th2 shift.As well as in the mice of overexpression of Trx-1 this shift was relieved.In summary,our present study showed that the addiction of METH decreased the expression of Trx-1 and induced immune balance to Th1 shift.The decreased expression of Trx-1 was restored in Trx-1 overexpression transgenic mice,and the Th1 shift was relieved.The addiction of MOR induced the expression of Trx-1 and induced immune balance to Th2 shift.The increased expression of Trx-1 was recovered in Trx-1 overexpression transgenic mice,and the Th2 shift was relieved,suggesting that Trx-1 has an important role in regulating the immune imbalance by MOR or METH.