Uncontrolled sepsis: a systematic review of translational immunology studies in intensive care medicine

David J Cain; Ana Gutierrez del Arroyo; Gareth L Ackland

doi:10.1186/2197-425X-2-6

Intensive Care Medicine Experimental

Table 8 Experimental conduct and exclusion criteria of monocyte tolerance studies

From: Uncontrolled sepsis: a systematic review of translational immunology studies in intensive care medicine

Author	Study population	Sample timing		Definition of sepsis	Microbiology results provided	Independent adjudication of sepsis diagnosis	Exclusion criteria immunosuppressive disease	Exclusion criteria malignancy	Primary conclusion of study (in relation to monocyte endotoxin tolerance)
Author	Study population	Time of first sample	No. of samples (time span)	Definition of sepsis	Microbiology results provided	Independent adjudication of sepsis diagnosis	Exclusion criteria immunosuppressive disease	Exclusion criteria malignancy
Liu [30]	Sepsis	?	1	? B C	N	N	N	N	TLR4 stimulation and human sepsis activate pathways that couple NAD⁺ and its sensor SIRT1 with epigenetic reprogramming
Buttenschoen [41]	Elective surgery	Pre-insult	4 (2 days)	N	N	N	Y	N	Cytokine liberation of mononuclear cells suggests a state of postoperative endotoxin tolerance
Pachot [31]	Sepsis	72 h (onset sep shock)	2	1C	Y	Y	N	N	CX3CR1 expression [is] severely down-regulated in [septic] monocytes and associated with lack of functionality
West [32]	Sepsis	24 h (ICU adm)	1	1 A, E	Y	N	N	N	Leukocytes of septic patients, but not SIRS, show LPS tolerance
Harter [33]	Sepsis	?	1	1 A B C	Y	Y	N	N	Endotoxin tolerance in septic patients does not depend solely on TLR-2 or TLR-4 expression
Flohe [40]	Surgery in trauma patients	48 h (ICU adm)	Mon, Thu.	1 A B C	Y	N	Y	Y	Initial trauma [and] major secondary surgery cause suppression of immune functions, whereas minor surgery does not
Escoll [34]	Sepsis	48 h (onset sepsis)	1	1 A	Y	Y	Y	Y	Monocytes from septic patients rapidly express IRAK-M mRNA when stimulated with LPS ex vivo [unlike healthy volunteers]
Heagy [39]	ICU patients (sepsis)	72 h (ICU adm)	1	5	N	Y	N	N	ICU patients with…endotoxin tolerance have significantly poorer clinical outcomes
Calvano [35]	Sepsis	?	1	1 E A	Y	N	N	N	Cellular LPS hyporesponsiveness [cannot] be ascribed to significant alterations in…cell surface LPS binding proteins
Sfeir [36]	Sepsis	24 (Sep Shock)	1	1C	Y	Y	Y	N	Monocytes from patients with septic shock exhibit persistent IL-10 release at a time when TNF-α release is down-regulated
Kawasaki [42]	Elective surgery	Pre-insult	7 (7 days)	N	N	N	Y	N	LPS responsiveness…is altered from the early period of surgery
Heagy [37]	Sepsis	72 h (ICU adm)	1	5	Y	Y	N	N	Impaired TNF release may be a manifestation of monocyte endotoxin tolerance and may be useful to diagnose sepsis
Bergmann [38]	Sepsis	?		1 B C	N	N	N	N	The altered [TNF-α release] of septic blood to catecholamines might be due to altered reactivity of leukocytes

Sample timing: Were control samples taken at the same time point after the inflammatory stimulus as subject samples? When was the first sample taken from the subject? How many samples were taken for each subject in total and over what time span? Sepsis criteria: The criteria used to enrol subjects into the study. Where subgroups of these criteria were used (e.g. septic shock) these are detailed. 0, not stated; 1, ACCP/SCCM 1992 Consensus Conference [73]; 2, ACCP/SCCM Consensus Conference 2001 [74]; 3, SSC Consensus Conference 2008 [75]; 4, CDC NNIC [86]; 5, Microbiology and clinical assessment; 6, Postmortem identification of infection; N, infection not considered; question mark (?), criteria not described. Sepsis severity groups enrolled: A = sepsis, B = severe sepsis, C = septic shock, D = acute renal failure, E = SIRS. Microbiology documentation: Were causative organisms clearly isolated and identified? Were additional steps taken to define whether the subject had sepsis beyond the initial clinical diagnosis, i.e. retrospective review of the case in light of subsequent information?

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