Comment on “IL-15 Prevents Apoptosis, Reverses Innate and Adaptive Immune Dysfunction, and Improves Survival in Sepsis” and Comment on “IL-7 Promotes T Cell Viability, Trafficking, and Functionality and Improves Survival in Sepsis”

I read with interest the articles by Hotchkiss et al. on IL-15 (1) and IL-7 (2) improving survival in sepsis, based on a mouse model of cecal ligation and puncture.

We measured plasma cytokines in Malawian children with severe bacterial infection, using a multiplex assay as part of a larger study (3, 4). IL-7R signaling is known to be deficient in HIV-infected individuals and inversely associated with age (5). In total, 155 children with severe bacterial infection had IL-7 and IL-15 measured on admission. The mortality was 25%, and 52% of children were HIV infected. There were 87 males (56%), and the median age was 2.4 y (IQR 0.67–7.0). Mean plasma IL-15 and IL-7 concentrations were significantly increased in survivors compared with nonsurvivors after controlling for HIV status, age, and neutrophil count (p = 0.017; p = 0.015, respectively).

The data published in The Journal of Immunology (1, 2) are exciting and promise new therapies for sepsis. Data from animal models of disease contribute greatly to our understanding of disease mechanisms, but these observations ultimately need to be confirmed in vivo and ex vivo in human subjects with severe sepsis. Our study was observational and not designed to examine T cell function in detail; however, our clinical data are supportive of the hypotheses that IL-7 and IL-15 improve survival in a population with both a high incidence of HIV and a high mortality from severe sepsis. Further functional work is needed in this population to confirm our preliminary findings.