Blood loss after trauma induces several systemic inflammatory responses culminating in the dysfunction and failure of organs. In this issue of the British Journal of Nutrition, Relja et al. ⁽Reference Relja, Töttel and Breig¹⁾ have examined the inflammatory signals at the subcellular, cellular and tissue levels after haemorrhage-induced hepatic injury and resuscitation in rats. Hepatic injury and resuscitation induced the expression of intercellular adhesion molecule-1, neutrophil infiltration and necrosis in the liver, and augmented serum alanine transaminase and IL-6 levels. It also induced IκBα phosphorylation and the activation of NF-κB. Pre-treatment with green tea extract (GTE: catechins >80 %, with >40 % of epigallocatechin gallate (EGCG)) suppressed the inflammatory responses at all levels, including neutrophil infiltration, intercellular adhesion molecule-1 expression and the release of IL-6, and, importantly, suppressed the activation of NF-κB.

The inflammatory responses occurring in the liver after haemorrhage are parallel to the inflammatory events occurring after inducing ischaemia, and EGCG is also active in the latter setting⁽Reference Giakoustidis, Giakoustidis and Iliadis^2–Reference Ichikawa, Matsui and Imai⁵⁾. The anti-inflammatory efficacy of EGCG demonstrated in all these studies generates a unifying hypothesis. Hepatic injury induced by ischaemia⁽Reference Giakoustidis, Giakoustidis and Iliadis²⁾ caused oxidative stress with enhanced production of reactive oxygen species and TNF-α; both mediated the expression of nuclear factors and kinases, activating the signal transduction pathways to trigger cell death. The liver that stained positive for NF-κB in the ischaemia group remained negative in the EGCG-pre-treated group. Neutrophil infiltration that was enhanced in the ischaemia group was significantly reduced after EGCG. Ischaemia-induced myocardial injury⁽Reference Aneja, Hake and Burroughs³⁾ also caused significant neutrophil infiltration, an increase in plasma IL-6, and activation of IκB kinase and NF-κB in the tissues. EGCG pre-treatment significantly reduced myocardial damage, neutrophil infiltration and plasma IL-6, and also suppressed the NF-κB pathway. Intestinal injury induced by ischaemia⁽Reference Giakoustidis, Giakoustidis and Koliakou⁴⁾ also resulted in an enhanced production of reactive oxygen species, neutrophil infiltration and activation of NF-κB. EGCG pre-treatment significantly deactivated NF-κB, decreased neutrophil infiltration and lowered reactive oxygen species production. All these studies support the conclusion derived by Relja et al. and collectively point out that induced inflammatory responses are mediated through NF-κB-dependent mechanisms, and EGCG per se or in combination with other catechins suppresses NF-κB activation and alleviates inflammation.

There are enumerable reports on the efficacy of EGCG per se or EGCG in combination with other catechins (epigallocatechin or epicatechin gallate or gallocatechin gallate)⁽Reference Ichikawa, Matsui and Imai^5–Reference Ludwig, Lorenz and Grimbo⁹⁾ on inflammatory responses induced by different exogenous and endogenous factors. The inflammatory inducers include polymicrobial sepsis⁽Reference Wheeler, Lahni and Hake¹⁰⁾, lipopolysaccharide⁽Reference Ichikawa, Matsui and Imai^5–Reference Yang, Oz and Barve^7, Reference Yang, de Villiers and McClain¹¹⁾, Staphylococcus aureus enterotoxin B⁽Reference Watson, Vicario and Wang¹²⁾, Helicobacter pylori infection⁽Reference Lee, Yeo and Choue¹³⁾, IL-1β alone⁽Reference Corps, Curry and Buttle^8, Reference Singh, Ahmed and Islam^14–Reference Wheeler, Catravas and Odoms¹⁶⁾ or in combination with β-amyloid⁽Reference Kim, Jeong and Lee¹⁷⁾ or oxygen tension⁽Reference Andriamanalijaona, Kypriotou and Baugé¹⁸⁾ or TNF-α⁽Reference Ludwig, Lorenz and Grimbo^9, Reference Heinecke, Grzanna and Au¹⁹⁾ or TNF-α alone⁽Reference Chen, Wheeler and Malhotra^20–Reference Lee, Jung and Kim²²⁾, UV-B⁽Reference Afaq, Adhami and Ahmad^23–Reference Song, Bi and Xu²⁵⁾, repetitive oxidative stress⁽Reference Sen, Chakraborty and Raha²⁶⁾, cigarette smoke condensate⁽Reference Syed, Afaq and Kweon²⁷⁾, phorbol 12-myristate 13-acetate⁽Reference Shin, Kim and Jeong^28–Reference Kundu and Surh³⁰⁾, trinitrobenenesulphonic acid⁽Reference Abboud, Hake and Burroughs³¹⁾- or acetic acid⁽Reference Ran, Chen and Xiao³²⁾-induced colitis, receptor activator for the NF-κB ligand⁽Reference Lin, Chen and Wang^33, Reference Lee, Jin and Shim³⁴⁾ or high glucose⁽Reference Wu, Wu and Huang³⁵⁾. Most importantly, all these studies document that consequent to the down-regulation of NF-κB pathways, EGCG or catechin combination suppressed the levels of several pro-inflammatory cytokines (TNF-α⁽Reference Yang, de Villiers and McClain^11, Reference Watson, Vicario and Wang^12, Reference Shin, Kim and Jeong^28, Reference Ran, Chen and Xiao^32, Reference Wu, Wu and Huang³⁵⁾ IL-6⁽Reference Kim, Jeong and Lee^17, Reference Xia, Song and Bi^24, Reference Shin, Kim and Jeong²⁸⁾, IL-8⁽Reference Wheeler, Catravas and Odoms^16, Reference Kim, Jeong and Lee^17, Reference Chen, Wheeler and Malhotra^20, Reference Syed, Afaq and Kweon^27, Reference Shin, Kim and Jeong²⁸⁾, interferon-γ⁽Reference Watson, Vicario and Wang^12, Reference Ran, Chen and Xiao³²⁾), chemokine (Fractalkine⁽Reference Lee, Jung and Kim²²⁾) and enzymes (matrix metaloproteinases-1, -3, -9⁽Reference Syed, Afaq and Kweon²⁷⁾, -13⁽Reference Corps, Curry and Buttle^8, Reference Ahmed, Wang and Lalonde^15, Reference Andriamanalijaona, Kypriotou and Baugé¹⁸⁾, NO synthase⁽Reference Lin and Lin^6, Reference Wheeler, Lahni and Hake^10, Reference Singh, Ahmed and Islam^14, Reference Song, Bi and Xu^25, Reference Syed, Afaq and Kweon^27, Reference Ran, Chen and Xiao³²⁾; cyclo-oxygenase-2⁽Reference Kim, Jeong and Lee^17, Reference Heinecke, Grzanna and Au^19, Reference Kundu and Surh³⁰⁾, glucosyl/lactosyl and Gb3 transferases⁽Reference Moon, Choi and Lee²¹⁾), growth factors (vascular endothelial growth factor⁽Reference Kim, Jeong and Lee¹⁷⁾), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin⁽Reference Ludwig, Lorenz and Grimbo⁹⁾) and monocyte chemotactic protein-1⁽Reference Hong, Kim and Chang²⁹⁾. In this regard, the study of Relja et al. is well justified in the use of GTE, since other tea catechins act synergistically with EGCG. It is important to use GTE with a greater percentage of EGCG to counteract inflammation. These preclinical studies on the induced inflammatory responses promote the hypothesis that green tea catechins have the potential to suppress the NF-κB-mediated inflammatory pathway into a salient concept relevant to nutritional management of inflammation. The emerging concept is that EGCG or GTE has the potential to block the NF-κB pathway, which plays a critical role in inflammation induced by various factors and also in malignancy. These aforementioned studies pave the way for phase I and II clinical trials using GTE or EGCG to control trauma, haemorrhage or ischaemia-induced inflammation.

There is no conflict of interest.