Association of the Hematopoietic Cytokine Interleukin-3 with the Systemic Host Immune Response in Critically Ill Patients with Acute Respiratory Failure
Year: 2021
Type: conference-abstract
Abstract: Rationale Interleukin-3 (IL-3) is hematopoietic cytokine that stimulates both progenitor cells and committed immune cells including macrophages, megakaryocytes, and granulocytes. In addition to roles in hematopoiesis, recent work has identified that IL-3 can be produced by specialized innate immune cells providing a proximal link between innate immune activation and IL-3 production. In preclinical murine sepsis studies, excessive IL-3 can drive "emergency hematopoiesis" recruiting immune cells from the bone marrow and driving cytokine storm. Clinical studies of IL-3 in critically ill patients are limited, with some suggesting that higher IL-3 levels are associated with higher mortality. In this study, we examined systemic IL-3 levels in critically ill patients with acute respiratory failure. Methods We performed a retrospective analysis of 160 patients enrolled in the Acute Lung Injury (ALI) Registry, a prospective cohort of patients with acute respiratory failure at the University of Pittsburgh. An expert panel classified subjects into one of three categories: acute respiratory distress syndrome [ARDS] (n=39); at risk for ARDS [ARFA] (n=91); or airway controls (n=30). We classified all subjects into "hyperinflammatory" or "hypoinflammatory" phenotypes by latent class analysis incorporating 10 host-response biomarkers as previously described. We subsequently assessed baseline plasma IL-3 levels using a multiplex assay. We determined: (1) associations of IL-3 with measures of the systemic immune response; (2) differences in IL-3 between hypoinflammatory and hyperinflammatory phenotypes; (3) differences in IL-3 levels between ARDS, ARFA, and airway control groups; and (4) associations between IL-3 and clinical outcomes. All analyses were performed using Stata version 15. Results IL-3 positively correlated with measures of innate immunity including IL-6 (r=0.373), IL-8 (r=0.491), IL-10 (r=0.360), and TNFr1 (r=0.273), p<0.001 for all. IL-3 levels were higher in patients in the hyperinflammatory phenotype (11.72pg/mL [6.19-27.80]) compared to hypoinflammatory phenotype (7.92pg/mL [5.90-13.54], p=0.003). Median IL-3 did not differ amongst ARDS (7.92pg/mL ), ) and control groups (6.00pg/mL [5.70-11.67]). IL-3 was not significantly associated with 30-day mortality (p=0.189) or ICU length of stay (p=0.351) with trend towards a negative association between IL-3 and ventilator-free days (OR = -2.054 [-4.258-0.149], P=0.067). Conclusions The hematopoietic cytokine IL-3 was significantly associated with markers of innate immunity. Elevated IL-3 levels in the hyperinflammatory ARDS phenotype are consistent with a potential role in driving "emergency hematopoiesis" and amplifying innate immune responses. Future studies are warranted to determine whether IL-3 could drive emergency hematopoiesis in critically ill patients with respiratory failure.
Institution: University of Pittsburgh Medical Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4248393340