reached because of the lack of studies of the relationship between immune function and lead in human adults and because most of the studies reported changes only in observational characteristics, such as immune-cell profiles or Ig concentrations, rather than effects on immune function (such as lymphocyte proliferation, phagocytosis of infectious agents, and NK tumoricidal activity), which is linked more closely with pathologic response or human disease. Even in those cases, however, there was inadequate evidence of an association owing to a general lack of investigations at lower BLLs and inconsistency in available data. The metric of bone lead could have been relevant in terms of a cumulative dose, but very few studies that examined changes in immune end points used non-BLL metrics.

Other Studies Considered

Alterations in the immune response that can be easily studied in humans are limited and are primarily reflective of changes in circulating leukocyte profiles and Ig concentrations. Some studies of lead-exposed workers have reported lead-associated differences in serum Ig concentrations, percentages of CD4+ TH cells, increased circulating B-lymphocytes, decreased NK cells, and impaired lymphoblastogenesis (Ewers et al. 1982; Horiguchi et al. 1992; Fischbein et al. 1993; Queiroz et al. 1993; Undeger et al. 1996; Pinkerton et al. 1998; Basaran and Undeger 2000; El-Safty and Metwally 2000; Kuo et al. 2001; Qiao et al. 2001; Ayatollahi 2002; Mishra et al. 2003, 2006; Heo et al. 2004; Valentino et al. 2007; Mishra et al. 2010; Garcia-Leston et al. 2011). In contrast, other human investigations at similar BLLs demonstrated opposite or no effects on the same characteristics (Horiguchi et al. 1992; Queiroz et al. 1994; Pinkerton et al. 1998; Heo et al. 2004; Mishra et al. 2006; Freije and Dairi 2009). Some results of relevant studies that demonstrated early immunotoxic effects in lead-exposed workers who had BLLs of 40 μg/dL or under are described in brief below.

El-Safty and Metwally (2000) found reduced serum IgA, IgM, and IgG concentrations in lead-exposed plumbers who had an average BLL of 39 μg/dL. Studies by Mishra et al. (2006) supported the finding on circulating Ig and further demonstrated that lead-exposed workers who had an average BLL over 10 μg/dL had increased serum IgA. Fischbein et al. (1993) reported alterations in circulating blood mononuclear-cell profiles and lymphocyte function in firearms instructors. Results of that highly relevant study demonstrated that people who had an average BLL of 25 μg/dL or under, and to a greater extent those who had a BLL over 25 μg/dL, had lower concentrations and lower functional integrity of CD4+ TH lymphocytes than healthy nonexposed controls. Specifically, the absolute percentage and number of CD3+ and CD4+ cells were statistically significantly reduced, whereas those of CD8+ cells were unchanged. Functional integrity of T cells, as determined by proliferative responses to mitogens, was impaired, whereas that of T-cell-dependent B-lymphocyte function appeared to be within the normal range at all stages of maturation. Another study (Sata et al. 1997) demonstrated that circulating immune cell profiles were increased in leadexposed male workers, concentrations of B lymphocytes were positively associated



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