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COMMENTARY
Year : 2017  |  Volume : 25  |  Issue : 1  |  Page : 23-25

Commentary to ‘Could serum cytokines serve as predictors in outcome of thermal burn injuries’


Department of Plastic, Reconstructive & Aesthetic Surgery, Indraprastha Apollo Hospitals, New Delhi, Delhi, India

Date of Web Publication13-Dec-2017

Correspondence Address:
Kuldeep Singh
Department of Plastic, Reconstructive & Aesthetic Surgery, Indraprastha Apollo Hospitals, New Delhi, Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijb.ijb_23_17

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How to cite this article:
Singh K. Commentary to ‘Could serum cytokines serve as predictors in outcome of thermal burn injuries’. Indian J Burns 2017;25:23-5

How to cite this URL:
Singh K. Commentary to ‘Could serum cytokines serve as predictors in outcome of thermal burn injuries’. Indian J Burns [serial online] 2017 [cited 2018 Aug 17];25:23-5. Available from: http://www.ijburns.com/text.asp?2017/25/1/23/217042

An inflammatory response is induced by major burns, which is characterized by the activation of inflammatory pathways and the release of various cytokines.[1] There are pro- and anti-inflammatory cytokines in a complex network. One cytokine can influence multiple cell types, or pleiotropy, and multiple cytokines can influence one cell type, or redundancy.[2]

The pro- and anti-inflammatory cytokines usually counterbalance each other. The uncontrolled release of these cytokines promotes immune dysfunction and severe systemic inflammation, which result in tissue damage, multi-organ failure or death in patients with burns.[1]

There have been various studies on the behaviour of cytokine levels in patients with burns, but the precise role of each cytokine, pathogenic or prognostic, has not been precisely identified.

Interleukin (IL)-1 is an endogenous pyrogen that induces several acute phase reactions. It induces IL-2-dependent T-cell proliferation, leading to specific antigen-dependent immune responses. It is also involved in stimulating or suppressing the production of other cytokines such as IL-6.[3]

IL-6 is a B-cell differentiation factor inducing antibody production, T-cell activation, the induction of hepatic acute phase protein synthesis, haematopoietic stimulation and tumour cell growth inhibition.[3]

Tumour necrosis factor (TNF) is known to cause tumour necrosis. It also stimulates fibroblasts, modulates granulopoiesis and affects bone resorption, haemostasis and lipid metabolism. It can induce the production of IL-6 and IL-1. It is thought to be a primary mediator of host response to inflammation.[3]

Drost et al.[3] measured the plasma levels of IL-1b, IL-6 and TNFa following burns. Cytokine levels in 27 patients were compared with 16 healthy controls. The cytokine levels were measured 3 times a week for 6 weeks. The percentage of samples with detectable levels of IL-1b and IL-6 were significantly higher (P < 0.05) in patients with burns than in controls. They found mean plasma IL-6 levels in non-survivors to be significantly higher (P < 0.001) when compared to surviving patients.

Temporal profile showed 90% of patients with detectable levels of IL-6 during the first week, declining to 50% in the fifth week post-burn. IL-1b also showed a similar trend. TNFa showed no such trend. Only IL-1b showed an increased percentage of positive samples with increasing burn size, with no apparent relationship in the case of IL-6 and TNFa.

The relationship between IL-6 and mortality was significant. Mean IL-6 levels were about 4-fold higher in non-survivors than survivors. Hack et al.[4] showed similar results in non-survivors vs survivors. Because IL-6 level decreased with time in the study by Drost et al. and did not show any relation with burn size, it was assumed to be related to early post-traumatic events.

de Bandt et al.[5] measured the plasma levels of IL-1b, TNFa and IL-6 in 12 patients with burns from day 2 to day 21 post-burn. Il-6 levels were increased in all patients throughout the study period, peaking on day 4 and correlated with burn injury size (P < 0.01). TNFa was also elevated, being significantly higher on day 7 in patients who developed sepsis (P < 0.05), but did not correlate with the extent of burn injury. IL-1b was rarely detected in their study.

Hur et al.[6] studied cytokine levels in 67 patients with burns on day 1 and day 3 assessing 27 different cytokines. They used 25 healthy volunteers as controls. They analyzed statistical differences in the concentration of each cytokine between control and patient groups between days 1 and 3, and between survival and non-survival groups for 27 cytokines.

They found IL-1 RA (Receptor Antagonist) not 1b, IL-6, 8, 10 and 15 or monocyte chemo-attractant protein (MCP)-1 levels among others to be significantly higher (P < 0.05) among patients with burns than in controls. IL-1RA and IL-6 levels were significantly higher (P < 0.05) in the non-survival group than in the survival group on day 1. They concluded that IL-1RA, IL-6 and MCP-1 might be used as prognostic indicators of mortality in patients with burns.

They found their results to be partly at variance with other studies in as far as IL-1b and IL-2, 4, 5, 7, 10, 12, 13 and 17 were concerned. They tried to explain this discrepancy on the basis of the influence of multiple other factors such as age, burn size, time after burn, comorbidities or complications, as well as the white blood cell (WBC) count. The up-regulated cytokines could be mediators induced directly by burns, secondary mediators or merely the markers of systemic inflammation, they postulated. IL-6 and IL-8 are pro-inflammatory cytokines, whereas IL-1RA and IL-10 are anti-inflammatory (immunomodulatory) cytokines. They suggested that not all pro-inflammatory cytokines are up-regulated, but there exists a system of checks and balances among the cytokine network.

Most cytokines in their study were up-regulated more on day 1 than day 3, except for IL-6.

Regarding mortality, their finding of significantly different levels of IL-1RA and IL-6 were in agreement with other studies. These, along with MCP-1, they concluded, might serve as prognostic indicators in patients with burn injury.

In the current study, IL-1b and IL-6 mirrored their change in levels over time (not seen in other studies) both in survivors as well as in non-survivors, as well as an increase in levels related to the extent of burn size. Herein, both IL-1b and IL-6 showed a positive correlation to total body surface area (TBSA) burn, which was at variance with other studies such as by Drost et al., in which IL-6 did not show any relationship to burn size. However, the authors of this study were in concurrence with a few observations in the study by de Bandt et al., in which IL-6 did show a correlation with increasing burn size, but surprisingly showed no detectable levels of IL-1b.

With regard to mortality in this study, both IL-1b and IL-6 showed a progressive increase in non-survivors compared to survivors, in whom both the Il-1b and IL-6 (P < 0.05) levels predictably decreased. Again, this was at variance with the findings of Drost et al., in which IL-6 showed a similar trend, but IL-1b showed no such trend. de Bandt et al. only found TNFa correlating with sepsis showing a progressive increase, but no such correlation for IL-1b or IL-6.

Hur et al. very interestingly found IL-6 levels to be significantly higher on day 1 itself in non-survivors as compared to survivors (P < 0.05), whereas the current study found no significant difference in the first sample on day 4 between the survivors and non-survivors.

Vindennes et al.[7] actually found much higher concentrations of IL-1b in those who survived compared to those who died (P = 0.005), which is at complete variance with this study.

Drost et al.[3] concluded that the fact that cytokines vary independently with respect to burn size and time post-burn suggests that their release into the circulation may be triggered by different mechanisms.

With so much variation among studies and so much of interplay between all cytokines, it is very difficult to bring out a clear significance of any single cytokine, except that IL-6 possibly could be a prognostic indicator if measured serially over time. There is much variation because of multiple factors and variables in patients with burns, and, perhaps, more standardized studies with strict control of various parameters may bring more clarity to the issue.

 
  References Top

1.
Finnerty CC, Herndon DN, Przkora R, Pereira CT, Oliveira HM, Queiroz DM et al. Cytokine expression profile over time in severely burned pediatric patients. Shock 2006;26:13-9.  Back to cited text no. 1
    
2.
Ozaki K. Cytokine and cytokine receptor pleiotropy and redundancy. J Biol Chem 2002;277:29355-8.  Back to cited text no. 2
    
3.
Drost AC, Burleson DG, Cioffi WG, Jordan BS, Mason AD, Pruitt BA. Plasma cytokines following thermal injury and their relationship with patient mortality, burn size and time post burn. J Trauma 1993;35:335-9.  Back to cited text no. 3
    
4.
Hack CE, De Groot ER, Felt-Berama RJ, Nuijens JH, Strack Van Schijndel RJ, Eerenberg-Belmer AJ et al. Increased plasma levels of interleukin-6 in sepsis. Blood 1989;74:1704-10.  Back to cited text no. 4
    
5.
de Bandt JP, Chollet-Martin S, Hernvann A, Lioret N, du Roure LD, Lim SK et al. Cytokine response to burn injury: Relationship with protein metabolism. J Trauma 1994;36:624-8.  Back to cited text no. 5
    
6.
Hur J, Yang HT, Chun W, Kim JH, Shin SH, Kang HJ et al. Inflammatory cytokines and their prognostic ability in cases of major burn injury. Ann Lab Med 2015;35:105-10.  Back to cited text no. 6
    
7.
Vindennes HA, Ulvestad E, Bjerknes R. Concentrations of cytokines in plasma of patients with large burns: Their relation to time after injury, burn size, inflammatory variables, infection, and outcome. Eur J Surg 1998;164:647-56.  Back to cited text no. 7
    




 

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