IL-21 Therapy Repaired Immune Function in Primate SIV Research Study

Future study into IL-21 urged.

When combined with antiretrovirals, interleukin 21 (IL-21) fusion protein reduced immune level activation and restored intestinal immune function in rhesus macaques with simian immunodeficiency virus (SIV), according to a study published in The Journal of Clinical Investigation.

Mirko Paiardini, PhD, postdoctoral fellow Luca Micci, PhD, and research specialist Emily Ryan from the Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University School of Medicine in Atlanta and colleagues reported the findings, which examined data on 16 rhesus macaques.

The researchers treated eight of the rhesus macaques with the IL-21 fusion protein starting two months after they were infected with SIV. All 16 macaques received antiretrovirals, and the eight controls received antiretroviral drugs only.

Antiretroviral drug treatment continued for seven months and then was withdrawn. IL-21 was given in three once-per-week cycles, including one cycle just after antiretroviral drugs were stopped.

SIV was detected in both study groups at the follow-up period, but in the eight macaques given IL-21, SIV RNA levels in blood samples were five times less than that of the control group. Viral DNA levels in blood CD4 T cells and intestinal tissue also were reduced. In addition, there was better immunity against microbes and immune activation was reduced in the IL-21 group.

In an interview with Infectious Disease Advisor, Dr Paiardini explained that “residual immune activation/inflammation is a very important problem for the clinical management of ART-treated HIV-infected individuals. In my opinion, the strongest and most relevant take away message from this study is that IL-21 reduces levels of immune activation. The other important consideration is that IL-21, alone or in combination with other interventions, is tested in clinical trials in cancer patients.”


1. Micci L, Ryan ES, Fromentin R, et al. Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques. J Clin Invest. 2015; DOI: 10.1172/JCI81400.