Expression Levels Of Plasma PD-1Related Cytokines In Patients With Different HIV-1 Infected Progression

Objective:In order to explore the change of plasma levels of PD-1 related cytokines[interferon gamma(IFN-γ),tumor necrosis factorα(TNF-α),interleukin-2(IL-2),IL-6,IL-10,and IL-15]in patients with different HIV-1 infected progression and it’s clinical significance on disease progression.Methods:According to the patients’informed consent and the review and approval of the ethics committee,10 patients with rapid progression of HIV-1 infection and 10 patients with slow progression of HIV-1 infection were selected from the cohort of acute HIV-1infections which was established in the past;and 20 healthy controls were selected.The levels of IFN-γ,TNF-α,IL-2,IL-6,IL-10,IL-15 in the plasma of HIV-1 infected patients in each group were detected by luminex liquid chip technology,and CD4~+T lymphcytes were measured by flow cytometry,and the viral load was determined by Roche Cobas Ampli Prep/cobas Taq Man48 high-sensitivity PCR detection system.We consult relevant data and analyze the test results.Results:1.The levels of IFN-γ(p=0.026),TNF-α(p=0.005),IL-2(p=0.008),IL-6(p=0.001),IL-10(p=0.003),IL-15(p=0.004)in the rapid disease progress group(RDPs)were significantly higher than those in the slow disease progress group(SDPs),and the levels of IFN–γ,TNF–α,IL-2,IL-6,IL-10,IL-15 in the HIV-1 infected group were significantly higher than those in the healthy control group;2.Compared with the RDPs,the levels of IFN-γ(p<0.001),TNF-α(p=0.03),IL-2(p=0.014),IL-6(p=0.003),IL-10(p=0.018),IL-15(p=0.006)in the SDPs for three years were significantly higher than those for 6 months;3.The folds of IFN-γ(r=0.452,p<0.001),IL-10(r=0.244,p=0.025)in the RDPs were positively correlated with viral load,there was no significant correlation between the folds of cytokine concentration and viral load in the SDPs,and the folds of IFN-γ(r=0.291,p<0.001),TNF-α(r=0.275,p<0.001),IL-6(r=0.261,p=0.001),IL-10(r=0.232,p=0.003)in HIV-1 infected patients were positively correlated with viral load as a whole;4.The folds of IFN-γ(r=-0.261,p=0.013)was negatively correlated with CD4~+T cell count in the RDPs,there was no significant correlation between the folds of cytokine concentration and CD4~+T cell count in the SDPs,and the folds of IFN-γ(r=-0.289,p<0.001),TNF-α(r=-0.203,p=0.008),IL-6(r=-0.260,p<0.001)and IL-10(r=-0.205,p=0.003)in HIV-1 infected patients were negatively correlated with CD4~+T cell count in the mass;5.The levels of above cytokines in the plasma of HIV-1 infected patients were positively correlated with each other:the levels of TNF-α(r=0.636,p<0.001),IL-2(r=0.394,p<0.001),IL-6(r=0.636,p<0.001),IL-10(r=0.533,p<0.001),IL-15(r=0.398,p<0.001)were positively correlated with IFN-γ;the levels of IL-2(r=0.769,p<0.001),IL-6(r=0.634,p<0.001),IL-10(r=0.864,p<0.001),IL-15(r=0.735,p<0.001)were positively correlated with TNF-α;the levels of IL-6(r=0.439,p<0.001),IL-10(r=0.718,p<0.001),IL-15(r=0.951,p<0.001)were positively correlated with IL-2;the levels of IL-10(r=0.558,p<0.001),IL-15(r=0.402,p<0.001)were positively correlated with IL-6;the levels of IL-10(r=0.753,p<0.001)were positively correlated with IL-15;6.The correlation between IFN-γand TNF-α(r=0.895 vs r=0.554,p<0.001),IL-2(r=0.960 vs r=0.211,p<0.001),IL-6(r=0.960 vs r=0.542,p<0.001),IL-10(r=0.974 vs r=0.365,p<0.001),IL-15(r=0.945 vs r=0.220,p<0.001),TNF-αand IL-2(r=0.890 vs r=0.699,p<0.001),IL-6(r=0.882 vs r=0.518,p<0.001),IL-10(r=0.895 vs r=0.801,p<0.001),IL-15(r=0.825 vs r=0.682,p<0.001),IL-2 and IL-6(r=0.923 vs r=0.241,p<0.001),IL-10(r=0.962 vs r=0.579,p<0.001),IL-6 and IL-10(r=0.977 vs r=0.349,p<0.001),IL-15(r=0.957 vs r=0.179,p<0.001),IL-10 and IL-15(r=0.961 vs r=0.638,p<0.001)in the SDPs was more significant than that in the RDPs,but the correlation between IL-2 and IL-15 in the RDPs was more significant than that in the SDPs(r=0.972 vs r=0.893,p<0.001).Conclusion:1.HIV-1 infection lead to the increase of the plasma PD-1 related cytokines interferon gamma(IFN-γ),tumor necrosis factorα(TNF-α),interleukin-2(IL-2),IL-6,IL-10,IL-15 and the augment of the cytokines in the RDPs is more remarkable which may be related to the immune regulation mechanism;2.there was a certain correlation between viral load and CD4~+T cell count and the cytokines;3.the interaction between the cytokines was enhanced,and the degree of correlation is closely related to the progression of HIV-1infection.