Cytokine changes in fatal cases of paraquat poisoning

Abstract

Cytokine-mediated inflammation is involved in the pathophysiology of paraquat toxicity. Nevertheless, few human studies have examined fluctuations in circulating cytokine levels. Blood samples were obtained from 21 patients with paraquat poisoning and compared to those of 18 healthy controls. All paraquat patients received a standard detoxification protocol composed of hemoperfusion, pulse therapies of methylprednisolone and cyclophosphamide, followed by dexamethasone therapy. Nonsurvivors not only had higher scores for the severity index of paraquat poisoning (P=0.004) but also presented with higher white blood cell counts (P=0.046) than survivors. Multiplex immunoassays revealed higher circulating levels of interleukin 2 (IL-2), interleukin 9 (IL-9), interleukin 10 (IL-10) and macrophage inflammatory protein-1 beta (MIP-1β) in survivors than in healthy controls. Furthermore, the circulating levels of interleukin 1 beta (IL-1β), IL-2, interleukin 5 (IL-5), interleukin 8 (IL-8), IL-9, IL-10, interleukin 12 (IL-12 p70), interleukin 17A (IL-17A), eotaxin, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein 10 (IP-10) and MIP-1β were higher in nonsurvivors than in healthy controls. Finally, the circulating levels of IL-1β and MCP-1 were higher in nonsurvivors than in survivors. Therefore, the observation of cytokine-mediated inflammation is in line with the detoxification protocol because glucocorticoids and cyclophosphamide are potent anti-inflammatory agents. Additionally, circulating levels of IL-1β and MCP-1 could serve as promising prognostic markers for patients with paraquat poisoning.

Keywords: Paraquat poisoning; cytokine; inflammation; mortality; multiplex immunoassays; severity index of paraquat poisoning.

Figure 1

Multiplex cytokine immunoassay. Circulating levels of IL-2, IL-9 and IL-10 were significantly higher in survivors of paraquat poisoning (n=7) than in healthy controls (n=18). Circulating levels of IL-1β, IL-2, IL-5, IL-8, IL-9, IL-10, IL-12 p70 and IL-17A were significantly higher in nonsurvivors of paraquat poisoning (n=14) than in healthy controls (n=18). Circulating levels of IL-1β were significantly higher in nonsurvivors of paraquat poisoning (n=14) than in survivors (n=7). Abbreviations: IL-1β, interleukin 1 beta; IL-2, interleukin 2; IL-5, interleukin 5; IL-8, interleukin 8; IL-9, interleukin 9; IL-10, interleukin 10; IL-12 p70, interleukin 12 p70; IL-17A, interleukin 17A.

Figure 2

Multiplex cytokine immunoassay. Circulating levels of MIP-1β were significantly higher in survivors of paraquat poisoning (n=7) than in healthy controls (n=18). Circulating levels of eotaxin, G-CSF, MCP-1, IP-10 and MIP-1β were significantly higher in nonsurvivors of paraquat poisoning (n=14) than in healthy controls (n=18). Circulating levels of MCP-1 were significantly higher in nonsurvivors of paraquat poisoning (n=14) than in survivors (n=7). Abbreviations: IP-10, interferon gamma-induced protein 10; G-CSF, granulocyte colony-stimulating factor; MCP-1, monocyte chemoattractant protein-1; MIP-1β, macrophage inflammatory protein-1 beta.

Figure 3

Multiplex cytokine immunoassay. Circulating levels of IL-2, IL-9, IL-10 and MIP-1β were significantly higher in survivors of paraquat poisoning (n=7) than in healthy controls (n=18). Circulating levels of IL-1β, IL-2, IL-5, IL-8, IL-9, IL-10, IL-12 p70, IL-17A, eotaxin, G-CSF, MCP-1, IP-10 and MIP-1β were significantly higher in nonsurvivors of paraquat poisoning (n=14) than in healthy controls (n=18). Circulating levels of IL-1β and MCP-1 were significantly higher in nonsurvivors of paraquat poisoning (n=14) than in survivors (n=7). Abbreviations: IL-1β, interleukin 1 beta; IL-2, interleukin 2; IL-5, interleukin 5; IL-8, interleukin 8; IL-9, interleukin 9; IL-10, interleukin 10; IL-12 p70, interleukin 12 p70; IL-17A, interleukin 17A; IP-10, interferon gamma-induced protein 10; G-CSF, granulocyte colony-stimulating factor; MCP-1, monocyte chemoattractant protein-1; MIP-1β, macrophage inflammatory protein-1 beta.