We appreciate the comments of Dr. Carrol concerning the work in our manuscript and read with interest his findings on circulating IL-7 and IL-15 concentrations in children with severe bacterial infection, many of whom were HIV positive. Furthermore, Dr. Carrol’s observations regarding increased circulating IL-7 and IL-15 in survivors versus nonsurvivors are intriguing and should be considered in light of the recent work by Crawley et al. (1), showing that soluble IL-7Rα was increased in HIV infection and that it inhibits IL-7 activity. It is possible that in certain settings quantitation of circulating IL-7 and soluble IL-7Rα will be necessary to determine the role of functional IL-7 deficiency in disease as well as to guide the use of IL-7 as a therapeutic tool (2).
Dr. Carrol also commented on performing functional studies, and in this regard, we are initiating in vitro studies to examine the effect of IL-7 in reversing the immunosuppression observed in blood incubation studies from patients with sepsis. We also agree wholeheartedly with Dr. Carrol’s comments that it is time to move forward with the use of IL-7 in areas of infectious disease, including bacterial sepsis. IL-7 is currently in multiple clinical trials in patients with HIV, cancer, and hepatitis C, and in bone marrow reconstitution after whole-body irradiation (3, 4). It has been well tolerated and rarely induces the hyperinflammatory “cytokine storm” condition that occurs with IL-2. There are risks with any new therapy; however, in our opinion, a greater risk lies in continuing on our current path in which the mortality of sepsis remains stubbornly high at 30–40% in most series (5). It is our goal to begin dose safety trials of IL-7 in patients with sepsis as soon as feasible.