Cytokine expression profile over time in burned mice

Abstract

The persistent inflammatory response induced by a severe burn increases patient susceptibility to infections and sepsis, potentially leading to multi-organ failure and death. In order to use murine models to develop interventions that modulate the post-burn inflammatory response, the response in mice and the similarities to the human response must first be determined. Here we present the temporal serum cytokine expression profiles in burned in comparison to sham mice and human burn patients. Male C57BL/6 mice were randomized to control (n=47) or subjected to a 35% TBSA scald burn (n=89). Mice were sacrificed 3, 6, 9, 12, 24, 48 hours and 7, 10, and 14 days post-burn; cytokines were measured by multi-plex array. Following the burn injury, IL-6, IL-1β, KC, G-CSF, TNF, IL-17, MIP-1α, RANTES, and GM-CSF were increased, p<0.05. IL-2, IL-3, and IL-5 were decreased, p<0.05. IL-10, IFN-γ, and IL-12p70 were expressed in a biphasic manner, p<0.05. This temporal cytokine expression pattern elucidates the pathogenesis of the inflammatory response in burned mice. Expression of 11 cytokines were similar in mice and children, returning to lowest levels by post-burn day 14, confirming the utility of the burned mouse model for development of therapeutic interventions to attenuate the post-burn inflammatory response.

Cimetidine enhances delayed-type hypersensitivity responses and serum interleukin (IL)-2, -10, -12, and IL-17 levels after burn injury in an animal model

“…Our results regarding diminished production of IL-2 and IL-12 after thermal trauma are consistent with finding reported in other studies (Schwacha, 2003;Finnerty et al, 2009;Li et al, 2009). The results of the present study also showed that the serum levels of IL-17 were decreased after burn injury.…”

“…Moreover, biphasic alterations were seen in serum TGFβ levels (i.e., significant decreases and increases at PBD 3 and PBD 14, respectively). These results are not completely in keeping with those of Finnerty et al (2009), that showed that, following burn injury, serum levels of IL-6, IL-1β, IL-17, KC, G-CSF, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α, RANTES, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased, while those of IL-2, -3, and -5 were decreased over a 14 day post-burn period. Varedi et al (2001) reported that plasma levels of TGFβ were elevated at PBD 6-8.…”

“…Some investigations noted that thermal injury resulted in suppressed IL-10 production while others noted higher levels Gauglitz et al, 2008). The results of one study in C57BL/6 mice showed that triphasic alterations in serum IL-10 levels occurred (i.e., significant decrease at 9 h post-burn, significant elevation beginning at PBD 1, and a return to normal at PBD 10) (Finnerty et al, 2009). IL-10 was first thought to be secreted only by T H 2 cells, but now is known to be produced by a variety of cell types-in particular, monocytes/macrophages and T-cell sub-types, including Tr1, T reg , and T H 1 cells.…”

“…It has been suggested that burn-induced DTH suppression reported could be attributed to a reduction in antigen-presenting capacity by APC (Wang and Liang, 2007), activation and proliferation of regulatory T-cells (Hanschen et al, 2011), diminished production of IL-2, IFNγ, and IL-12 (Schwacha, 2003;Finnerty et al, 2009;Li et al, 2009), higher production of immunomodulatory cytokines such as TGFβ and IL-10 (Varedi et al, 2001;Finnerty et al, 2009), and/or overall reductions in T H 1 responses (Miller et al, 2007). Moreover, several cells involved in propagating the DTH response have been seen to be affected by thermal burn.…”

Increased muscle expression of interleukin-17 in Duchenne muscular dystrophy

“…Interestingly, however, IL-17 has recently been shown to be up-regulated at early time points in an experimental burn model. 33 The possible pathogenic role of IL-17 in inflammatory myositis and in muscle damage remains to be established. In this respect, we found that in DMD muscle increased levels of IL-17 were associated with higher expression levels of the inflammatory cytokines TNF-␣ and MCP-1.…”