Levels of IL-6 and soluble IL-6 receptor are increased in HIV patients with a history of immune restoration disease after HAART.
OBJECTIVE
We have previously described immune restoration diseases (IRD) associated with asymptomatic opportunistic infections presenting in immunodeficient HIV patients responding to highly active antiretroviral therapy (HAART). Here we address the question of whether patients with a history of IRD exhibit persistent immune activation, shown by elevated levels of interleukin-(IL)-6 and soluble IL-6 receptor (sIL-6R).


METHODS
Peripheral blood mononuclear cells (PBMCs) and plasma were collected from HIV patients with nadir CD4 T cell counts of < 80/microL and who had achieved immune reconstitution after HAART with (n=14) or without (n=15) experiencing IRD, severely immunodeficient (SID) patients with < 80 CD4 T cells/microL (n=8) and HIV seronegative controls (n=15). PBMC production and plasma levels of IL-6, sIL-6R and interferon (IFN)-gamma (PBMC only) were measured by enzyme linked immunosorbent assay (ELISA). Intracellular flow cytometry was used to determine the predominant cellular source of IL-6 in HIV patients and controls.


RESULTS
Unstimulated PBMC from IRD patients produced significantly higher amounts of IL-6 and sIL-6R than non-IRD patients and HIV seronegative controls. The sIL-6R concentration was also significantly higher in supernatants from mitogen-stimulated PBMC from IRD patients compared to non-IRD patients. The production of IFN-gamma did not differ between IRD and non-IRD patients. IRD patients had significantly higher plasma levels of IL-6 compared to non-IRD patients, SID patients and controls. Monocytes were the predominant source of IL-6 in both HIV patients and controls.


CONCLUSIONS
Patients with a history of IRD after HAART have elevated levels of IL-6 and sIL-6R.
Stone
S F
SF
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital and Department of Pathology, University of Western Australia, Perth, Australia. Shelley.Stone@health.wa.gov.au
Price
P
P
Keane
N M
NM
Murray
R J
RJ
French
M A
MA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000097:blood / Q000276:immunology*; D018709:Statistics, Nonparametric
D015850:Interleukin-6; D012367:RNA, Viral; D019947:Receptors, Interleukin-6; D007371:Interferon-gamma