Journal Article

Multicentric experience with interferon gamma therapy in sepsis induced immunosuppression. A case series

Miatello, Jordi, Pickkers, Peter, Payen, Didier, Faivre, Valerie, Tissières, Pierre, Lukaszewicz, Anne Claire, Dupuis, Claire, Leentjens, Jenneke, Brumpt, Caren

2019

Overview

Background The sepsis-induced immunodepression contributes to impaired clinical outcomes of various stress conditions. This syndrome is well documented and characterized by attenuated function of innate and adaptive immune cells. Several pharmacological interventions aimed to restore the immune response are emerging of which interferon-gamma (IFNγ) is one. It is of paramount relevance to obtain clinical information on optimal timing of the IFNγ-treatment, −tolerance, −effectiveness and outcome before performing a RCT. We describe the effects of IFNγ in a cohort of 18 adult and 2 pediatric sepsis patients. Methods In this open-label prospective multi-center case-series, IFNγ treatment was initiated in patients selected on clinical and immunological criteria early (< 4 days) or late (> 7 days) following the onset of sepsis. The data collected in 18 adults and 2 liver transplanted pediatric patients were: clinical scores, monocyte expression of HLA-DR (flow cytometry), lymphocyte immune-phenotyping (flow cytometry), IL-6 and IL-10 plasma levels (ELISA), bacterial cultures, disease severity, and mortality. Results In 15 out of 18 patients IFNγ treatment was associated with an increase of median HLA-DR expression from 2666 [IQ 1547; 4991] to 12,451 [IQ 4166; 19,707], while the absolute number of lymphocyte subpopulations were not affected, except for the decrease number of NK cells 94.5 [23; 136] to 32.5 [13; 90.8] (0.0625)]. Plasma levels of IL-6 464 [201–770] to 108 (89–140) ng/mL ( p  = 0.04) and IL-10 from IL-10 from 29 [12–59] to 9 [1–15] pg/mL decreased significantly. Three patients who received IFNγ early after ICU admission (<4 days) died. The other patients had a rapid clinical improvement assessed by the SOFA score and bacterial cultures that were repeatedly positive became negative. The 2 pediatric cases improved rapidly, but 1 died for hemorrhagic complication. Conclusion Guided by clinical and immunological monitoring, adjunctive immunotherapy with IFNγ appears well-tolerated in our cases and improves immune host defense in sepsis induced immuno suppression. Randomized clinical studies to assess its potential clinical benefit are warranted.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adult / Aged / Aged, 80 and over / Bacterial and fungal diseases / Biological response modifiers / Care and treatment / Child / Child health / Clinical trials / Cytokines / Depression (Mood disorder) / Enzyme-linked immunosorbent assay / Female / HLA-DR Antigens - metabolism / Humans / Immune response / Immune Tolerance / Immuno-depression / Immunotherapy / Infant / Infection / Infectious Diseases / Intensive Care Units / Interferon / Interferon gamma / Interferon-gamma - therapeutic use / Interleukin-10 - blood / Interleukin-6 - blood / Internal Medicine / Killer cells / Killer Cells, Natural - cytology / Killer Cells, Natural - metabolism / Life Sciences / Liver / Liver transplantation / Lymphocyte immuno-phenotyping / Lymphocytes / Male / Medical Microbiology / Medical research / Medicine / Medicine & Public Health / MHC class II / Middle Aged / Monocytes - cytology / Monocytes - metabolism / Mortality / Organ transplantation / Parasitology / Pediatrics / Prospective Studies / Pseudomonas aeruginosa - isolation & purification / Research Article / Sepsis / Sepsis - drug therapy / Sepsis - microbiology / Tropical Medicine