A population-based assessment of blood lead levels in relation to inflammation $ Natthapol Songdej a , Paul C Winters a , Michael J McCabe Jr b , Edwin van Wijngaarden a,b,n a Department of Community and Preventive Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA b Department of Environmental Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA article info Article history: Received 1 April 2009 Received in revised form 16 December 2009 Accepted 23 December 2009 Available online 29 January 2010 Keywords: Lead Inflammation C-reactive protein White blood cell count Gender differences abstract Background: Some experimental and observational research suggests that inflammation may be an important mediator of lead toxicity. However, lead-induced inflammation has not been well-studied in non-occupationally exposed populations. Methods: Using data for 9,145 individuals Z40 years of age from the National Health and Nutrition Examination Survey 1999–2004, we assessed the association between blood lead levels (BLLs) and C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) count via ordinal logistic regression. We also examined the interaction between BLL and gender in relation to the inflammatory markers. Results: No evidence for an association between lead exposure and inflammatory markers was observed with odds ratios around or below the null. Although men but not women appeared to be at increased risk of lead-induced inflammation, no consistent dose-response patterns were observed across BLL quintiles. Conclusion: Inflammation does not appear to be an important mediator of lead toxicity. & 2010 Elsevier Inc. All rights reserved. 1. Introduction Blood lead levels (BLLs) below 10 mg/dL have been shown to exert adverse multisystemic health effects, and involves the hematopoietic, renal, vascular, reproductive, neurological, gastro- intestinal, endocrine, and immunologic systems (Barth et al., 2002; Canfield et al., 2003; Kosnett et al., 2007; Monnet-Tschudi et al., 2006; Muldoon et al., 1996; Nigg et al., 2008; Papanikolaou et al., 2005; Payton et al., 1998; Rodrı ´guez-Iturbe et al., (2005); Schwartz and Otto, 1991; Wright et al., 2003; Y¨ ucesoy et al., 1997). Inflammation is thought to play a role in the etiology of most of these health outcomes (Blay et al., 1992; Erlinger et al., (2004); Hefler et al., 2008; Lee et al., 2001; Margolis et al., 2007; McSorley et al., 2007; Mora et al., 2006; Napoli et al., 2001; Nozoe et al., 2001; Pradhan et al., 2001; Ridker 2007; Schaumberg et al., 2007; Seddon et al., 2004; Sesso et al., 2003; Schmid et al., 2007; Shankar et al., 2007; Vozarova et al., 2002), suggesting that inflammation may be a mediator of the multisystemic toxicity of lead. Indeed, both animal and human studies have shown a relationship between lead exposure and proinflammatory cyto- kines, in one study at blood lead levels below background values in humans (Iavicoli et al., 2006). For example, lead exposed rats produce higher levels of the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and inter- leukin-1-beta (IL-1b) within the brain than non-lead exposed rats (Struzynska et al., 2007; Kishikawa and Lawrence, 1998). In addition, lead exposed rats experience higher activation of nuclear factor-kappa B in the kidney than non-lead exposed rats (Rodrı ´guez-Iturbe et al., 2005). Increased expression and produc- tion of inflammatory markers in association with lead exposure have also been found in humans. Occupationally exposed workers have increased levels of interferon gamma, a cytokine that plays a role in macrophage activation, and TNF-alpha when compared to a non-occupationally exposed group (Mishra et al., 2003). However, only one study has described the relationship between lead levels and inflammatory markers in a non-occupationally exposed population, who experience much lower levels of lead exposure than exposed workers. Kim and colleagues evaluated this relationship in a sample of 300 healthy South Korean University students and found that, with certain genotypes, there are increased levels of TNF-alpha, IL-6, and white blood cell (WBC) count in men (there were very few female participants) with a BLL Z2.51 mg/dL (Kim et al., 2007). Using data from the National Health and Nutrition Examina- tion Survey (NHANES) 1999 À2004, we examined the association ARTICLE IN PRESS Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/envres Environmental Research 0013-9351/$ - see front matter & 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.envres.2009.12.008 $ The study was reviewed by the Research Subjects Review Board at the University of Rochester and was deemed to be exempt due to secondary use of pre-existing data under Study # RSRB00023795. There were no funding sources that supported this study. n Corresponding author at: Department of Community and Preventive Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 644, Rochester, NY 14642, USA. Fax: + 1 585 461 4532. E-mail address: edwin_van_wijngaarden@urmc.rochester.edu (E.v. Wijngaarden). Environmental Research 110 (2010) 272–277