The Immune Pathogenesis of Immune Reconstitution Inflammatory Syndrome Associated with Highly Active Antiretroviral Therapy in AIDS

Abstract

The present study investigated the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) in acquired immunodeficiency syndrome (AIDS) patients undergoing highly active antiretroviral therapy (HAART). A total of 238 patients with AIDS who received initial HAART were included in this prospective cohort study. Blood samples were collected immediately, at baseline, at week 12, and at week 24 after initial HAART and at the onset of IRIS. Lymphocyte subsets, Th1 and Th2 cytokines, and interleukin (IL)-7 levels were measured by flow cytometry or ELISA. Among the 238 patients with AIDS who received HAART, 47 patients developed IRIS. The percentages of CD4 + and CD8 + naive, memory, and activated cells exhibited no significant differences between AIDS patients with and without IRIS 24 weeks after initial HAART. The percentage of CD4 + CD25 + Foxp3 + regulatory T cells was lower in IRIS patients than in non-IRIS patients before HAART, 12 weeks after HAART, 24 weeks after HAART, and at the onset of IRIS. IL-2 and interferon (IFN)-c levels were significantly higher at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. In contrast, IL-4 and IL-10 levels were significantly lower at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. Plasma IL-7 decreased gradually with the progression of HAART. The level of IL-7 was higher in IRIS patients than in non-IRIS patients at all follow-up time points. An imbalance of Th1/Th2 cytokines, a consistently low CD + CD25 + Fox3 + percentage, and a high IL-7 level may be crucial in the pathogenesis of IRIS in AIDS patients who had received HAART.

Chemokine and Cytokine Cascade Caused by Skewing of the Th1-Th2 Balance Is Associated with High Intracranial Pressure in HIV-Associated Cryptococcal Meningitis

“…Serum cytokines and/or chemokines have emerged as important players in the development of HICP in HCM patients in recent years, but the related findings are inconsistent. For example, a study by Boulware et al indicated that high serum pre-ART levels of IL-4 and IL-17 are predictive of future IRIS in HCM patients [11], whereas Zheng's research indicated that decreased IL-4 and IL-17 levels were associated with HICP during IRIS [12]. These paradoxical research findings indicate the need to investigate further the roles of cytokines/chemokines in HICP.…”

Understanding Mechanisms Underlying the Pathology of Immune Reconstitution Inflammatory Syndrome (IRIS) by Using Animal Models

“…Particularly due to high levels of IL-12, TNFα, IFNγ, Th1 responses are considered to associate with IRIS. Other studies suggested that the imbalance between anti-inflammatory T regulatory cells (T regs ) and pro-inflammatory Th17 cells may also play a role in IRIS [16, 1, 17]. However, albeit inflammatory, the role of Th17 cells, in IRIS is still largely elusive.…”

Patogénesis del VIH/SIDA.

“…Por otro lado, recientemente han sido observadas personas infectadas con una cepa recombinante de VIH (CXCR-4 o R4) que presentan una rápida evolución de la infección a etapas avanzadas (sida) en menos de 3 años. (38,39) El TARV ha reducido de manera importante la morbi-mortalidad en VIH/sida.…”