Evaluation of Tumor Necrosis Factor-Alphaand Granulocyte Colony-Stimulating Factor Serum Levels in Lead-Exposed Smoker Workers

Abstract

Inorganic lead (Pb) is able to modulate the immune response even at low to moderate exposure levels. It inhibits in vitro and in vivo activities of neutrophilleucocytes and influences their blood count in humans. Neutrophil functions are governed by a number of cytokines. Pb has been shown to affect leukocyte production of some ofthese cytokines in vitro. The objective ofthis study is to assess serum tumor necrosis factor-alpha (TNF-a) and granulocyte colony-stimulating factor (G-CSF) levels of thirty-three male lead-exposed (E) workers at a lead recycling plant as compared with twenty-eight male non-exposed (NE) workers at a food processing plant, whose current smoking habit was known. Serum TNF-a and G-CSF levels were measured by a quantitative sandwich enzyme immunoassay. Blood lead levels (Pb-B) were significantly higher in E (geometric mean (GM) 30.7 pg/dl, GSD 1.7; min-max: 9.1-81.6 pg/ dl) workers than controls (GM 3.6 pg/dl, GSD 1.7; min-max: 1.0-11.0pg/dl). E workers had significantly higher serum TNF-a (median: 107.1; min-max: 11.1-623.0 pg/ml) and G-CSF levels (median: 53.0, min-max: 31.1-197.0 pg/ml) than NE workers (TNF-a: median: 12.0; min-max: 9.4-18.8 pg/ml; G-CSF: median: 34.3, min-max: 25.1-52.2 pg/ml). In particular, the TNF-a level was shown to be significantly influenced by lead exposure and smoking habit, as well as by interaction between these two factors. Both serum TNF-a and G-CSF levels were correlated with Pb-B and absolute neutrophil count. This study is the first to detect higher serum levels of G-CSF in E over NE workers. Our data confirm that exposure to low to medium doses of lead may interfere in the complex cytokine network involved in inflammation, especially in workers who are current smokers.

Analysis of lead toxicity in human cells

“…We demonstrated that lead exposures resulted in a dose-dependent increase of IL-8 production by PBMC as well as enhanced the production of the proinflammatory cytokines IL-6, TNF-α and the chemokines IL-8 and MIP-1α in response to mitogens. The increase in the TNF-α level was in agreement with previous studies [42] and was consistent with epidemiological data on lead-exposed workers [43]. Our observation that lead increases mitogenic activation of PBMC was in agreement with the activation of lymphocyte and leukocyte proliferation and function by lead which has been observed in earlier studies [24-27].…”

The effect of subacute lead exposure on selected blood inflammatory biomarkers and angiogenetic factors

“…However, the level of IL-6 did not change in this study. Similar results were obtained in lead recycling plant workers (BLL =30.7 μg/d l ), who exhibited significantly higher TNF-α than controls 19) . Our previous study on chronically Pb exposed workers (BLL=37.0 μg/d l ) demonstrated not only higher levels of TNF-α, but also higher levels of IL-6 and IL-1β 14) .…”

Ubiquitous hazardous metal lead induces TNF-α in human phagocytic THP-1 cells: Primary role of ERK 1/2

“…TNF-␣ is one of the principal mediators of the inflammatory responses in mammals, transuding deferential signals that regulate activation, proliferation and apoptosis at cellular levels [7]. Earlier studies identified the capacity of Pb to increase production of various pro-inflammatory cytokine mainly TNF-␣ among phagocytic cells of both animal and human [8][9][10][11][12], While the production of TNF-␣ can be elevated following exposure to lead, the expression of the receptor for TNF-␣ was also increased during the in vitro exposure of human blood monocytes to PbCl 2 [13]. Therefore, the combined effect of elevated cytokine production by macrophages and of increased receptor expression would be expected to contribute to problematic inflammatory responses.…”