| Purpose:Cryptococcal Meningitis(CM),an infection of the central nervous system caused by Cryptococcal neoplasm,is one of the most common opportunistic infections in the late stage of Acquired Immune Deficiency Syndrome(AIDS).Despite the widespread clinical use of antiretroviral therapy(ART)and antifungal drugs,CM is still an important cause of death in AIDS patients.The immune system of human body has a very close relationship with the nervous system.When central nervous system infection occurs,the levels of various cytokines in the body will be abnormal.Understanding the host immune response to Cryptococcus neoformans infection is of great significance for the rational development of immunoregulatory therapy.In this paper,we conducted a prospective study to regularly detect CSF cytokines of subjects,mainly to analyze the differences of cytokines among the three groups of HIV-positive patients with cryptococcal meningitis(HIV+CM+),HIVpositive patients with non-cryptococcal meningitis(HIV+CM-),and HIV-negative patients with non-cryptococcal meningitis(HIV-CM-)at baseline and the characteristics and dynamic changes of Th1/Th2 cytokine immune responses in patients with HIV combined with CM during treatment.The aim is to provide a scientific basis for the immunoregulatory therapy of HIV/AIDS patients with CM,improve the level of clinicians in the diagnosis and treatment of this disease,and reduce the mortality rate.Methods:Patients with HIV complicated with CM admitted to the Infection Department of You’an Hospital from January 2019 to October 2020 were selected as the case group.All patients were confirmed as HIV antibody positive by Western Blot(WB),and confirmed as CM patients by CSF stain or Cryptococcus culture.At the same time,HIV infected persons without central nervous system infection during the same period,non-HIV infected persons without central nervous system infection who were screened for neurosyphilis in the infected center,whose age matched with HIV+CM+ patients were enrolled as the control group.Patients in both control group and case group received lumbar puncture at baseline,and the CSF was collected for routine,biochemical and cytological tests.During the hospitalization of HIV+CM+ patients,CSF samples were collected dynamically every2 weeks.The CSF levels of Th1 cytokines IFN-γ,TNF-α,IL-2,IL-15 and Th2 cytokines IL-4,IL-6,IL-10,IL-13 were quantitatively analyzed by enzyme linked immunosorbent assay(ELISA)method.The SPSS 25.0 software was used for statistical analysis of the basic characteristics of the included population.Statistical analysis of cytokines between the three groups was performed in Graph Pad Prism V8.0(Graph Pad,La Jolla,California).Results:A total of 12 HIV+CM+,6 HIV+CM-,and 17 HIV-CM-were recruited for the study.Compared with HIV-CM-,the baseline cyclinal fluid IFN-γ,TNF-α,IL-10 and IL-15 level in HIV+CM+ patients were significantly higher(p=0.024,p<0.001,p=0.001,p=0.001),IL-4 level was significantly lower(p<0.001).Compared with HIV+CM-,the levels of TNF-αand IL-10 in HIV+CM+ patients were significantly higher(p=0.004,p=0.01).The IL-4levels of HIV+CM-patients were significantly lower than HIV-CM-(p=0.01),and IL-15 level was significantly higher(p=0.001).In addition to the above five cytokines,there is no significant difference between IL-2,IL-6,IL-13 among the three groups.Equation analysis showed low levels of IL-6(p=0.036)and IL-2(p=0.013)relative to baseline CSF cytokines at week 2,with no significant change at week 4.In addition,there were no significant differences in levels of all cytokines between survivors and deaths(all p>0.05)Conclusion:Our study found that the levels of IFN-γ and IL-15 in CSF of HIV+CM+ patients were higher than those of HIV-CM-,the levels of TNF-α and IL-10 were higher than those of HIV+CM-and HIV-CM-patients.We found that the level of IL-4 in CSF of HIV+CM+patients was lower than HIV-CM-.Compared with baseline CSF cytokines and chemokines,IL-2 and IL-6 levels were lower at week 2,and there is no evidence of Th1/Th2 imbalance,Th1 and Th2 cytokines may have a synergistic effect,however,due to too few included patients and short follow-up time,this result may not have much relevance to clinical outcomes. |
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