Impact of Environmental Contamination on Immunity: Implications for ...

Commentary

Impact of Environmental Contamination on Immunity: Implications for Childhood Vaccination Policy Bruce D. Forrest, MD, MBA Forrest & Company, Inc. PO Box 444 Nyack, NY 10960-0444 USA [email protected]

Introduction “Gates Foundation makes a bold investment in childhood vaccines” effectively summarizes the remarkable decision by the Bill and Melinda Gates Foundation to commit $10 billion to childhood vaccines.1 There is little doubt that the initial investment of just $750 million a decade ago achieved more than most other parties involved in pediatric public health in significantly reducing childhood mortality from vaccine preventable infectious diseases, whether directly or through stimulating an awareness of what could be possible with the right support and focus. One such commitment brought to the children of Rwanda a national immunization program using a pneumococcal conjugate vaccine against invasive pneumococcal disease.2 However, successes such as these in eliminating or reducing the established barriers of access to otherwise prohibitively expensive interventions for developing and emerging countries does expose other factors in such communities that can impact the value of these interventions through reducing the maximum benefit that can be obtained. Historically, underperforming vaccines or reductions in vaccine efficacy in developing communities has been 5

As the barriers to access to routine vaccines for children in the poorest countries in the world are eroded by the contributions of a range of donors, these successes expose other factors that can impact the value of these interventions. This is especially so in those communities that are concurrently experiencing rapid industrial growth. Such growth is frequently associated with escalating environmental contamination that even the lowest levels is known to significantly impair fundamental immune functions. Maximizing the value of this new access to vaccines also must address the effects of existing and future environmental contamination. However, there remains a gap between science, public health policy and community access in understanding how this might impact a community and how best to deliver on creating an environment that optimizes the value of this improved access to new vaccines for children. Keywords. immunity, vaccines, environmental contamination, pollution, pediatrics, infectious disease J Heath Pollution 1:5-7 (2011)

attributed to the short list of usual suspects of maternal education, vaccine distribution, nutrition, or intercurrent infections. Yet while evidence continues to accumulate on the modulating effects of environmental contaminants (such as organochlorines, oxymetholone, lead, cadmium, mercury and gallium arsenide) on immunity and the development of effective immune responses to pathogens or vaccines, rarely is this factor considered when optimizing a community or even national program of immunization.3–8 This is ironic as many countries that stand to benefit from the opportunities to secure access to novel vaccines are also in a transitional development phase associated with rapid industrial growth that is frequently accompanied by elevations in environmental contamination. The immune system appears especially sensitive to environmental contaminants such as lead, mercury, and cadmium,6,9 and while lead and cadmium exposures at low and

Blacksmith Institute Journal of Health & Pollution Vol. 1, No. 1 — Feb 2011

moderate levels do not produce overt cellular cytotoxicity, the immuneassociated health effects are a result of an impaired regulation of cell function, such that its detection and understanding requires the use of more sensitive indicators of immune function such as biomarkers.5,10 Understanding how specific environmental agents impair both immune function and the ability of the immune system to elicit protective immune responses is essential given the commitment of many funding bodies and agencies to eradicate vaccine-preventable infectious disease. It remains an unanswered question as to whether environmental contamination contributes to a significant reduction in vaccine efficacy. Understanding how environmental contamination may impair the development of immune responses in children becomes essential given that children’s immune systems have been recognized as being potentially more susceptible to environmental exposures.11

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Commentary

Impact of Environmental Contamination on Immunity: Implications for Childhood Vaccination Policy

Lead, and to a lesser extent cadmium, have been the most extensively studied in understanding how heavy metals impair immune function. While the overall effects of lead on antibody production appears to be minimal, if lead dosage and exposure are sufficient it can lead to depressed total antibody levels. More importantly low-level lead exposure skews antibody isotype production eliciting a more significant health risk. In effect, lead results in switching of B lymphocytes from producing IgM and IgG antibody isotopes critical in conferring protection against infectious agents to IgE associated with allergic and hypersensitivity responses, especially among children.5,12–14 However, it is the T lymphocyte subset that appears to be the most sensitive to the toxic effects of lead and cadmium, and to some extent gallium arsenide. Cadmium at sub-micromolar levels is known to both inhibit proliferation and directly induce apoptosis of CD4+ T lymphocytes,15 while gallium has a very specific role in inducing a defect in the early antigen-processing,3 and lead inhibits antigen presentation through inhibiting specific T lymphocytes (Th1) stimulation while promoting presentation to Th2 lymphocytes.8,16 By any of these mechanisms, the overall effect is to skew the immune response away from making protective antibody responses against specific pathogens and may impair the ability of a child with even low exposure levels to make an adequate immune response to a vaccine. Immune responses are known to be influenced by specific genes (eg, Vβ and Km(1)) that have been associated in some populations with increased susceptibilities to bacteria such as Haemophilus influenzae type b, pneumococcus, and meningococcus.17,18 That lead and mercury have been shown to bias usage of specific genes is of concern

Forrest

in populations already struggling with high vaccine-preventable disease rates and underlying genetic factors of susceptibility.19 Lead clearly plays a key role in the disruption of the critical Th1/Th2 lymphocyte balance necessary to maintain host resistance to infectious disease. Further, the production of a critical cytokine, interferon-γ, essential in the ability to initiate and maintain protective immune responses, and that has been recently demonstrated in young children under 3 years of age in Thailand and the Philippines to be associated with vaccine-induced protection against influenza,20 has been shown to be significantly impaired by lead and mercury exposure.4,21 Other cytokines important in eliciting protective responses are also significantly affected, such as interleukin (IL)-12 and IL-2. Both being significantly down-regulated to levels known to be inadequate for effective host resistance.22

One of the leading effects of lead is the suppression of the ability to induce delayed type hypersensitivity (DTH) responses upon exposure to a new antigen. Essentially, to elicit a protective immune response requires the induction of a DTH response to recruit lymphocytes and other cells to the site of the deposition of the antigen or vaccine. This impairment is the oldest of the known effects of lead on the immune response.23 As our knowledge concerning the underlying mechanisms of immune dysfunction associated with even low levels of environmental contaminants increases, it has become evident that even for a well studied and relatively common contaminant such as lead the levels required to down-regulate the basic immune functions is lower than the 10 µg/dl level above which is attributed to impaired intellectual development in children.6 However, what is evident is that while most attention has focused


6

Commentary on the effects of materials such as lead on intellectual development, induction of hypersensitivity reactions (e.g. asthma, skin rashes, etc.) and autoimmune disease, that the same underlying immune dysfunctions also have a critical impact in the effective implementation of routine pediatric vaccination programs and their likely effectiveness in communities involving even low levels of environmental heavy metal contaminants. A comprehensive three pronged effort: 1. addressing sources of

contamination

2. remediating any legacy

contamination from the past, and 3. medically managing and monitoring affected community members, including chelating when necessary is essential for any abatement program to work. Incomplete responses have a history of being ineffective, even in developed countries.24 A greater effort is needed to support research into understanding the practical effects of even low levels of environmental contamination on the ability to elicit and maintain

appropriate vaccine immunity in children if the efforts of donors to assure unprecedented access to new vaccines are to deliver on the promise of creating an environment that optimizes the value that these agents can deliver. This is especially true in rapidly developing parts of the world where the scale of toxic pollution is rapidly increasing, vaccine preventable disease remains a significant burden, and vaccination programs are relied upon to save lives.

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