Prognostic Value of Cytokines in Sirs General Medical Patients

Rodrı́guez-Gaspar, Melchor; Santolaria, Francisco; Jarque-López, A.; González‐Reimers, Emilio; Milena, Antonio; Vega, Marı́a-José de la; Rodrı́guez-Rodrı́guez, Eva; Gómez-Sirvent, Juan-Luis

doi:10.1006/cyto.2001.0932

Cited by 84 publications

(51 citation statements)

References 15 publications

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“…As noted previously, about 1/6 of the sequences identified in this study correspond to genes that were previously reported to be affected by EHI (Sonna et al 2004). Furthermore, of the 12 sequences for which the expression response to temperature was affected by clinical diagnosis in this study, at least three correspond to proteins that have been found by others to display different levels of expression in serum obtained from patients with sepsis vs. noninfectious SIRS:interleukin 8 (Rodriguez-Gaspar et al 2001), lipopolysaccharide binding protein (Prucha et al 2003), and HSP 70 (Adib-Conquy and Cavaillon 2007). Finally, housekeeping genes reported to show stable expression after exertional hyperthermia in vivo in a prior work (Sonna et al 2004) also showed stable expression with respect to temperature and clinical diagnosis in this study.…”

Section: Discussionsupporting

confidence: 74%

Core temperature correlates with expression of selected stress and immunomodulatory genes in febrile patients with sepsis and noninfectious SIRS

Sonna

Hawkins

Lissauer

et al. 2010

Cell Stress and Chaperones

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Environmental hyperthermia and exercise produce extensive changes in gene expression in human blood cells, but it is unknown whether this also happens during febrile-range hyperthermia. We tested the hypothesis that heat shock protein (HSP) and immunomodulatory stress gene expression correlate with fever in intensive care unit patients. Whole blood messenger RNA was obtained over consecutive days from 100 hospitalized patients suffering from sepsis or noninfectious systemic inflammatory response syndrome (SIRS) as defined by conventional criteria. The most abnormal body temperature in the preceding 24 h was recorded for each sample. Expression analysis was performed using the Affymetrix U133 chip. ANCOVA followed by correlation analysis was performed on a subset of 278 prospectively identified sequences of interest. Temperature affected expression of 60 sequences, either independently or as a function of clinical diagnosis. Forty-eight of these (representing 38 genes) were affected by temperature only, including several HSPs, transcription factors heat shock factor (HSF)-1 and HSF-4, cellular adhesion molecules such as ICAM1/CD54 and JAM3, toll receptors TLR-6 and TLR-7, ribosomal proteins, and a number of molecules involved in inflammatory pathways. Twelve sequences demonstrated temperature-dependent responses that differed significantly between patients with sepsis and noninfectious SIRS: CXCL-13; heat shock proteins DNAJB12 and DNAJC4; the F11 receptor; folate hydrolase 1; HSF-2; HSP 70 proteins HSPA1A, HSPA1B, and HSPA1L; interleukin 8; lipopolysaccharide binding protein; and prostaglandin E synthase. Febrile-range temperatures achieved during sepsis and noninfectious SIRS correlate with detectable changes in stress gene expression in vivo, suggesting that fever can activate HSP gene expression and modify innate immune responses. For some genes, it appears that clinical condition can alter temperature-sensitive gene expression. Collectively, these data underscore the potential importance of body temperature in shaping the immune response to infection and injury.

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Section: Discussionsupporting

confidence: 74%

Core temperature correlates with expression of selected stress and immunomodulatory genes in febrile patients with sepsis and noninfectious SIRS

Sonna

Hawkins

Lissauer

et al. 2010

Cell Stress and Chaperones

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“…There is a well described correlation between serum IL-6 levels and poor outcome in sepsis (8,(23)(24)(25)(26), and increased IL-6 is an independent predictor of survival in human sepsis (27). In our mouse model, serum IL-6 and IL-1␤ were markedly attenuated by exogenous CO administration.…”

Section: Discussionmentioning

confidence: 51%

Suppression of Inflammatory Cytokine Production by Carbon Monoxide Involves the JNK Pathway and AP-1

Morse

Pischke

Zhou

et al. 2003

Journal of Biological Chemistry

340

280

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The stress-inducible protein heme oxygenase-1 provides protection against oxidative stress and modulates pro-inflammatory cytokines. As the sepsis syndrome results from the release of pro-inflammatory mediators, we postulated that heme oxygenase-1 and its enzymatic product CO would protect against lethality in a murine model of sepsis. Mice treated with a lethal dose of lipopolysaccharide (LPS) and subsequently exposed to inhaled CO had significantly better survival and lower serum interleukin (IL)-6 and IL-1␤ levels than their untreated counterparts. In vitro, mouse macrophages exposed to LPS and CO had significantly attenuated IL-6 production; this effect was concentration-dependent and occurred at a transcriptional level. The same effect was seen with increased endogenous CO production through overexpression of heme oxygenase-1. Mutation within the AP-1-binding site in the IL-6 promoter diminished the effect of CO on promoter activity, and treatment of macrophages with CO decreased AP-1 binding in an electrophoretic mobility shift assay. Electrophoretic mobility supershift assay indicated that the JunB, JunD, and c-Fos components of AP-1 were particularly affected. Upstream of AP-1, CO decreased JNK phosphorylation in murine macrophages and lung endothelial cells. Mice deficient in the JNK pathway had decreased serum levels of IL-6 and IL-1␤ in response to LPS compared with control mice, and no effect of CO on these cytokine levels was seen in Jnk1 or Jnk2 genedeleted mice. In summary, these results suggest that CO provides protection in a murine model of sepsis through modulation of inflammatory cytokine production. For the first time, the effect of CO is shown to be mediated via the JNK signaling pathway and the transcription factor AP-1.

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“…Interestingly, confusion is an associated factor with increased levels of the pro-inflammatory cytokine IL-6, while arterial hypotension has a stronger association with increased levels of the anti-inflammatory cytokine IL-10. Moreover, in patients with severe sepsis or septic shock, increased IL-10 levels in blood were associated with a poorer prognosis [12][13][14][15]. Hyponatraemia and hyperglycaemia were associated with increased levels of different cytokines: hyponatraemia with IL-6, and hyperglycaemia with IL-10.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with inflammatory cytokine patterns in community-acquired pneumonia

Martínez¹,

Menéndez²,

Reyes³

et al. 2010

European Respiratory Journal

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Raised systemic levels of interleukin (IL)-6 and IL-10 cytokines have been associated with poorer outcome in community-acquired pneumonia. The aim of our study was to identify potential associated factors with increased levels of IL-6, IL-10, or both cytokines.We performed a prospective study of 685 patients admitted to hospital with communityacquired pneumonia. IL-6 and IL-10 were measured in blood in the first 24 h.30-day mortality increased from 4.8% to 11.4% (p50.003) when both cytokines were higher than the median. Independent associated factors with an excess of IL-6 were neurologic disease, confusion, serum sodium ,130 mEq?L -1 , pleural effusion, and bacteraemia. The associated factors for an excess of IL-10 were respiratory rate o30 breaths?min -1, systolic blood pressure ,90 mmHg and glycaemia o250 mg?dL -1 . The independent associated factors for an excess of both cytokines were confusion, systolic blood pressure ,90 mmHg, pleural effusion and bacteraemia. Protective factors were prior antibiotic treatment and pneumococcal vaccination.Different independent factors are related to an excess of IL-6 and IL-10. Confusion, hypotension, pleural effusion and bacteraemia were associated with the inflammatory profile with the highest mortality rate, whereas anti-pneumococcal vaccination and previous antibiotic treatment appeared to be protective factors.

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Prognostic Value of Cytokines in Sirs General Medical Patients

Cited by 84 publications

References 15 publications

Core temperature correlates with expression of selected stress and immunomodulatory genes in febrile patients with sepsis and noninfectious SIRS

Core temperature correlates with expression of selected stress and immunomodulatory genes in febrile patients with sepsis and noninfectious SIRS

Suppression of Inflammatory Cytokine Production by Carbon Monoxide Involves the JNK Pathway and AP-1

Factors associated with inflammatory cytokine patterns in community-acquired pneumonia

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