Wise Young
11-24-2006, 02:17 AM
Has there been any connection with thimerasol as a potential inhibitor to neural cell regenration? thanks
jverrill,
I have moved your thread to the Science Forum for further discussion.
As you know, thimerosal (sometimes referred to as thiomersal) is an organomercury compound that has been used as a preservative in vaccines produced by Eli Lilly and other companies. It is an anti-fungal and anti-bacterial compound that is toxic to cells. From the mid-1980's, most whole cell DPT and hepatitis vaccines that are administered to young children contained this compound. Due to claims that this compound may be contributing to neurological diseases, including autism in children, there have been calls for removal of thiomersal from all pediatric vaccines. Although thimerasol has been discontinued in some pediatric vaccines, the US FDA has concluded that the low doses of the thiomersal is not toxic to children and unused vaccine stocks containing thiomersal will not be recalled. Meanwhile the World Health Organization is continuing to provide thimerosal-containing vaccines to children around the world (Source (http://en.wikipedia.org/wiki/Thimerosal)). The FDA has a detailed FAQ regarding thimerosal (Source ( http://www.fda.gov/cber/vaccine/thimfaq.htm#q5)Source[/url]).
In micromolar concentrations, thimerosal is toxic to cells. The question is whether nanomolar concentrations of thimerosal due to vaccine injection is harmful. Parran, et al. (Parran, et al., 2005) assessed the effects of thimerosal on neurobastoma cells (a type of neural tumor cell) and found that 48 hour exposure to thimerosal causes cell death with a EC50 (the concentration at which half of the cells would die) of 4.35 nanomolar (nM) concentration. In the presence of nerve growth factor, the EC50 was 105 nM. This suggests that neuroblastoma cells are exquisitely sensitive to thiomerosal and the nerve growth factor reduced this sensitivity.
One theory is that thimerosal increases methallothionein and antibodies against methallothionein. Singh and Hanson (Singh and Hanson, 2006) studied methallothionein and antibodies against the protein in children with and without autism exposed to vaccine-derived thimerosal. They found no difference between the control and thimerosal exposed groups.
Another theory is that mercury induces autoimmune responses. Thimerosal induce autoimmune responses in mice (Havarinasab, et al., 2006). Thimerosal reduces TH2 responses by changing cytokine secretion by human dendritic cells (Agrawal, et al., 2006). Evidence of autoimmunity as a cause of autism and other neurodevelopmental disorders is very limited. Havarinasab, et al. (Havarinasab, et al., 2005) gave 10 mg/L of thimerosal in the drinking water for 30 days to A.SW (H-2) mice that are known to be very suceptible to autoimmune diseases. During the 30 days of treatment, the mice showed immunosuppression and this was superceded by a period of increased autoimmunity. The mice were exposed to mercury resulting in 81 microgram/gram in the urine at 14 days.
Much of the angst and controversy has been driven by several papers published by Geier & Geier in the last year or two. They (Geier and Geier, 2006) reported significantly increased risks of autism, speech disorders, mental retardation, personality disorders, thinking abnormalities, ataxia, and neurodevelopment disorders associated with exposure to TCV. In another study, they (Geier and Geier, 2006) reported a significant downward trend of neurodevelopmental disorders in the United States following removal of thimerosal from vaccines. It is important to note that neither of these studies are controlled studies and therefore do not provide rigorous and convincing data of cause-and-effect.
Very little or no evidence that suggests that low dose thimerosal would affect neuronal regeneration. I found only one study that reported that thimerosal increases calcium in olfactory ensheathing glia. For example, Hayat, et al. (Hayat, et al., 2003) reported that thimerasol increases intracellular calcium in olfactory ensheathing glia but this is at doses that far exceed those that would be produced by a vaccine and it is not clear how this would prevent regeneration.
Both the FDA and WHO have concluded that there is no credible evidence that the very low doses contained in vaccine injections are harmful. Some studies suggest that low concentrations of thimerosal may have cellular effects. For example, thimerosal is an IP3 receptor sensitizer that may affect mouse embryonic cells (Kapur, et al., 2006). Walker, et al. (Walker, et al., 2006) have reported that thimerosal increases heat shock protein RNA levels in cultured lymphocytes from autistics children but these occur at 10 micromolar ethyl mercury concentrations. Most studies that show toxic effects involve thimerosal at micromolar concentrations, much higher than the exposure levels from thimerosal containing vaccines (TCV).
I am not an expert on thimerosal and have by no means conducted an exhaustive analysis of the research in this field. However, it seems unlikely that very low doses of thimerosal caused the positive correlation of neurodevelopmental disorders and vaccines and the downturn in such disorders after discontinuation of the thimerosal containing vaccine. I say this for the following reasons.
First, if such a low one-time dose of ethyl mercury contributes a significant risk of autism and neurodevelopment disorders, one would see a huge upsurge of these problems whenever and wherever mothers and children have been exposed to ethyl mercury. Ethyl mercury, for example is present in many fish and other products. It has been used for many years as a topical disinfectant for cuts and wounds, e.g. mercurochrome. Although fears of mercury exposure has led the FDA to discontinue it in the U.S., it is still used all around the world. We don’t have a rash of autism and other neurodevelopment disorders after such exposures.
Second, mercury induces expression of heat-shock protein (HSP) and metallothionein. Both of these are expressed by partly injured cells. HSP is neuroprotective while metallothionein stimulates regeneration. The theory that antibodies develop against these two proteins not only is not supported by evidence but doesn’t make sense. If so, this would imply that every time a child gets a bump or bruise, he or she would have a higher risk of autism and other neurodevelopmental disorders. This is not only not so but doesn't make sense.
In summary, I am skeptical that low-doses of thiomerosal will have any effect on regeneration of neurons.
References
Kapur N, Mignery G and Banach K (2006). Cell Cycle Dependent Calcium Oscillations in Mouse Embryonic Stem Cells. Am J Physiol Cell Physiol During cell cycle progression, somatic cells exhibit different patterns of intracellular calcium signals during the G0 phase, the transition from G1 to S and from G2 to M. Because pluripotent embryonic stem (ES) cells progress through cell cycle without the gap-phases G1 and G2 we aimed to determine if ES cells still exhibit characteristic changes of [Ca(2+)]i during cell cycle progression. With confocal imaging of the Ca-sensitive dye Fluo-4/AM we identified that undifferentiated mES-cells exhibit spontaneous Ca-oscillations. In control cultures where 50.4 % of the cells reside in the S-phase of the cell cycle, oscillations appeared in 36 % of the cells within a colony. Oscillations were not initiated by Ca-influx but depended on IP3 mediated Ca-release and the refilling of intracellular stores by a store operated Ca-influx (SOC) mechanism. Using cell cycle synchronization, we determined that Ca-oscillations were confined to the G1/S phase (~70% oscillating cells vs. G2/M: ~15 % oscillating cells) of the cell cycle. ATP induced Ca-oscillations, and activation of SOC entry could be induced in G1/S and G2/M synchronized cells. Intracellular Ca-stores were not depleted and all three IP3 receptor isoforms were present throughout the cell-cycle. Cell cycle analysis after EGTA, BAPTA/AM, 2-APB, thapsigargin or U-73122 treatment, underlined that IP3 mediated Ca release is necessary for cell cycle progression through G1/S. Because the IP3 receptor sensitizer thimerosal induced Ca-oscillations only in G1/S we propose that changes in IP3R sensitivity or basal levels of IP3 could be the basis for the G1/S confined Ca oscillations. Key words: embryonic stem cell, cell cycle, Calcium oscillation, IP3. Physiology, Loyola Univ. Chicago, Maywood, Illinois, United States. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17092997
Walker SJ, Segal J and Aschner M (2006). Cultured lymphocytes from autistic children and non-autistic siblings up-regulate heat shock protein RNA in response to thimerosal challenge. Neurotoxicology 27: 685-92. There are reports suggesting that some autistic children are unable to mount an adequate response following exposure to environmental toxins. This potential deficit, coupled with the similarity in clinical presentations of autism and some heavy metal toxicities, has led to the suggestion that heavy metal poisoning might play a role in the etiology of autism in uniquely susceptible individuals. Thimerosal, an anti-microbial preservative previously added routinely to childhood multi-dose vaccines, is composed of 49.6% ethyl mercury. Based on the levels of this toxin that children receive through routine immunization schedules in the first years of life, it has been postulated that thimerosal may be a potential triggering mechanism contributing to autism in susceptible individuals. One potential risk factor in these individuals may be an inability to adequately up-regulate metallothionein (MT) biosynthesis in response to presentation of a heavy metal challenge. To investigate this hypothesis, cultured lymphocytes (obtained from the Autism Genetic Resource Exchange, AGRE) from autistic children and non-autistic siblings were challenged with either 10 microM ethyl mercury, 150 microM zinc, or fresh media (control). Following the challenge, total RNA was extracted and used to query "whole genome" DNA microarrays. Cultured lymphocytes challenged with zinc responded with an impressive up-regulation of MT transcripts (at least nine different MTs were over-expressed) while cells challenged with thimerosal responded by up-regulating numerous heat shock protein transcripts, but not MTs. Although there were no apparent differences between autistic and non-autistic sibling responses in this very small sampling group, the differences in expression profiles between those cells treated with zinc versus thimerosal were dramatic. Determining cellular response, at the level of gene expression, has important implications for the understanding and treatment of conditions that result from exposure to neurotoxic compounds. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27156, USA. swalker@wfubmc.edu http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16870260
Singh VK and Hanson J (2006). Assessment of metallothionein and antibodies to metallothionein in normal and autistic children having exposure to vaccine-derived thimerosal. Pediatr Allergy Immunol 17: 291-6. Allergic autoimmune reaction after exposure to heavy metals such as mercury may play a causal role in autism, a developmental disorder of the central nervous system. As metallothionein (MT) is the primary metal-detoxifying protein in the body, we conducted a study of the MT protein and antibodies to metallothionein (anti-MT) in normal and autistic children whose exposure to mercury was only from thimerosal-containing vaccines. Laboratory analysis by immunoassays revealed that the serum level of MT did not significantly differ between normal and autistic children. Furthermore, autistic children harboured normal levels of anti-MT, including antibodies to isoform MT-I (anti-MT-I) and MT-II (anti-MT-II), without any significant difference between normal and autistic children. Our findings indicate that because autistic children have a normal profile of MT and anti-MT, the mercury-induced autoimmunity to MT may not be implicated in the pathogenesis of autism. Department of Biology, Utah State University, Logan, UT 84322, USA. singhvk@cc.usu.edu http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16771783
Havarinasab S, Bjorn E, Ekstrand J and Hultman P (2006). Dose and Hg species determine the T-helper cell activation in murine autoimmunity. Toxicology Inorganic mercury (mercuric chloride-HgCl(2)) induces in mice an autoimmune syndrome (HgIA) with T cell-dependent polyclonal B cell activation and hypergammaglobulinemia, dose- and H-2-dependent production of autoantibodies targeting the 34kDa nucleolar protein fibrillarin (AFA), and systemic immune-complex deposits. The organic mercury species methylmercury (MeHg) and ethylmercury (EtHg-in the form of thimerosal) induce AFA, while the other manifestations of HgIA seen after treatment with HgCl(2) are present to varying extent. Since these organic Hg species are converted to the autoimmunogen Hg(2+) in the body, their primary autoimmunogen potential is uncertain and the subject of this study. A moderate dose of HgCl(2) (8mg/L drinking water-internal dose 148mugHg/kg body weight [bw]/day) caused the fastest AFA response, while the induction was delayed after higher (25mg/L) and lower (1.5 and 3mg/L) doses. The lowest dose of HgCl(2) inducing AFA was 1.5mg/L drinking water which corresponded to a renal Hg(2+) concentration of 0.53mug/g. Using a dose of 8mg HgCl(2)/L this threshold concentration was reached within 24h, and a consistent AFA response developed after 8-10 days. The time lag for the immunological part of the reaction leading to a consistent AFA response was therefore 7-9 days. A dose of thimerosal close to the threshold dose for induction of AFA (2mg/L drinking water-internal dose 118mugHg/kgbw per day), caused a renal Hg(2+) concentration of 1.8mug/g. The autoimmunogen effect of EtHg might therefore be entirely due to Hg(2+) formed from EtHg in the body. The effect of organic and inorganic Hg species on T-helper type 1 and type 2 cells during induction of AFA was assessed as the presence and titre of AFA of the IgG1 and IgG2a isotype, respectively. EtHg induced a persistent Th1-skewed response irrespectively of the dose and time used. A low daily dose of HgCl(2) (1.5-3mg/L) caused a Th1-skewed AFA response, while a moderate dose (8mg/L) after 2 weeks resulted in a balanced or even Th2-skewed response. Higher daily doses of HgCl(2) (25mg/L) caused a balanced Th2-Th1 response already from onset. In conclusion, while metabolically formed Hg(2+) might be the main AFA-inducing factor also after treatment with EtHg, the quality of the Hg-induced AFA response is modified by the species of Hg as well as the dose. Molecular and Immunological Pathology (AIR), Department of Molecular and Clinical Medicine, Linkoping University, SE-581 85 Linkoping, Sweden. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17084957
Agrawal A, Kaushal P, Agrawal S, Gollapudi S and Gupta S (2006). Thimerosal induces TH2 responses via influencing cytokine secretion by human dendritic cells. J Leukoc Biol Thimerosal is an organic mercury compound that is used as a preservative in vaccines and pharmaceutical products. Recent studies have shown a TH2-skewing effect of mercury, although the underlying mechanisms have not been identified. In this study, we investigated whether Thimerosal can exercise a TH2-promoting effect through modulation of functions of dendritic cells (DC). Thimerosal, in a concentration-dependent manner, inhibited the secretion of LPS-induced proinflammatory cytokines TNF-alpha, IL-6, and IL-12p70 from human monocyte-derived DC. However, the secretion of IL-10 from DC was not affected. These Thimerosal-exposed DC induced increased TH2 (IL-5 and IL-13) and decreased TH1 (IFN-gamma) cytokine secretion from the T cells in the absence of additional Thimerosal added to the coculture. Thimerosal exposure of DC led to the depletion of intracellular glutathione (GSH), and addition of exogenous GSH to DC abolished the TH2-promoting effect of Thimerosal-treated DC, restoring secretion of TNF-alpha, IL-6, and IL-12p70 by DC and IFN-gamma secretion by T cells. These data suggest that modulation of TH2 responses by mercury and Thimerosal, in particular, is through depletion of GSH in DC. Division of Basic and Clinical Immunology, University of California, Irvine, California, USA. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17079650
Geier DA and Geier MR (2006). A meta-analysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 in the United States. Neuro Endocrinol Lett 27: BACKGROUND: Thimerosal is an ethylmercury-containing compound (49.6% mercury by weight) used as at the preservative level in vaccines (0.005% to 0.01%). METHODS: Statistical modeling in a meta-analysis epidemiological assessment of the Vaccine Adverse Event Reporting System (VAERS) for neurodevelopment disorders (NDs) reported following Diphtheria-Tetanus-whole-cell-Pertussis (DTP) vaccines in comparison to Diphtheria-Tetanus-whole-cell-Pertussis-Haemophilus Influenzae Type b (DTPH) vaccines (administered: 1994-1997) and following Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP), vaccines in comparison to Thimerosal-free DTaP vaccines (administered: 1997-2000), was undertaken. RESULTS: Significantly increased adjusted (sex, age, vaccine type, vaccine manufacturer) risks of autism, speech disorders, mental retardation, personality disorders, thinking abnormalities, ataxia, and NDs in general, with minimal systematic error or confounding, were associated with TCV exposure. CONCLUSION: It is clear from the results of the present epidemiological study and other recently published data associating mercury exposure with childhood NDs, additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially from Thimerosal-containing vaccines. Vice-President, The Institute for Chronic Illnesses, Inc. (Silver Spring, MD 20905), USA. mgeier@comcast.net. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16807526
Geier DA and Geier MR (2006). An assessment of downward trends in neurodevelopmental disorders in the United States following removal of Thimerosal from childhood vaccines. Med Sci Monit 12: CR231-9. BACKGROUND: The US is in the midst of an epidemic of neurodevelopmental disorders (NDs). Thimerosal is an ethylmercury-containing compound added to some childhood vaccines. Several previous epidemiological studies conducted in the US have associated Thimerosal-containing vaccine (TCV) administration with NDs. MATERIAL/METHODS: An ecological study was undertaken to evaluate NDs reported to the Vaccine Adverse Event Reporting System (VAERS) from 1991 through 2004 by date of receipt and by date of vaccine administration. The NDs examined included autism, mental retardation, and speech disorders. Statistical trend analysis was employed to evaluate the effects of removal of Thimerosal on the proportion of NDs reported to VAERS. RESULTS: There was a peak in the proportion of ND reports received by VAERS in 2001-2002 and in the proportion of ND reports by date of vaccine administration in 1998. There were significant reductions in the proportion of NDs reported to VAERS as Thimerosal was begun to be removed from childhood vaccines in the US from mid-1999 onwards. CONCLUSIONS: The present study provides the first epidemiological evidence showing that as Thimerosal was removed from childhood vaccines, the number of NDs has decreased in the US. The analysis techniques utilized attempted to minimize chance or bias/confounding. Additional research should be conducted to further evaluate the relationship between TCVs and NDs. This is especially true because the handling of vaccine safety data from the National Immunization Program of the CDC has been called into question by the Institute of Medicine of the National Academy of Sciences in 2005. Department of Biochemistry, George Washington University, Washington, DC, USA. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16733480
Hayat S, Wigley CB and Robbins J (2003). Intracellular calcium handling in rat olfactory ensheathing cells and its role in axonal regeneration. Mol Cell Neurosci 22: 259-70. Intracellular calcium handling by rat olfactory ensheathing cells (OECs) is implicated in their support for regrowth of adult CNS neurites in a coculture model of axonal regeneration. Pretreatment of OECs with BAPTA-AM to sequester glial intracellular calcium ([Ca(2+)](i)) reduces significantly the numbers of cocultured neurons regrowing neurites. The mean resting [Ca(2+)](i) of OECs cultured alone or with neurons was 300 nM in an external solution containing 2.5 mM calcium ([Ca(2+)](o)). In high [K(+)](o) or zero [Ca(2+)](o), resting [Ca(2+)](i) significantly decreased. [Ca(2+)](i) significantly increased when [Ca(2+)](o) was increased to 20 mM, lonomycin, thapsigargin, and thimerosal increased [Ca(2+)](i), and caffeine, ryanodine, and cyclopiazonic acid were without effect. Of the receptor agonists tested, none induced a change in [Ca(2+)](i). The calcium influx induced by high [Ca(2+)](o) was blocked by La(3+) and SKF96365, partially inhibited by Cd(2+), and insensitive to Ni(2+) and nifedipine. Pretreatment of OECs with La(3+) reduced neurite regrowth in cocultures in a concentration-dependent manner over the range that blocked the non-voltage-gated calcium flux through a putative TRP-like channel, which, we propose, is activated in OEC-mediated axonal regeneration. Neural Damage and Repair GroupCentre for Neuroscience Research, King's College London, Guys Campus, SE1 1UL, London, UK http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12676535
Parran DK, Barker A and Ehrich M (2005). Effects of thimerosal on NGF signal transduction and cell death in neuroblastoma cells. Toxicol Sci 86: 132-40. Signaling through neurotrophic receptors is necessary for differentiation and survival of the developing nervous system. The present study examined the effects of the organic mercury compound thimerosal on nerve growth factor signal transduction and cell death in a human neuroblastoma cell line (SH-SY5Y cells). Following exposure to 100 ng/ml NGF and increasing concentrations of thimerosal (1 nM-10 microM), we measured the activation of TrkA, MAPK, and PKC-delta. In controls, the activation of TrkA MAPK and PKC-delta peaked after 5 min of exposure to NGF and then decreased but was still detectable at 60 min. Concurrent exposure to increasing concentrations of thimerosal and NGF for 5 min resulted in a concentration-dependent decrease in TrkA and MAPK phosphorylation, which was evident at 50 nM for TrkA and 100 nM for MAPK. Cell viability was assessed by the LDH assay. Following 24-h exposure to increasing concentrations of thimerosal, the EC50 for cell death in the presence or absence of NGF was 596 nM and 38.7 nM, respectively. Following 48-h exposure to increasing concentrations of thimerosal, the EC50 for cell death in the presence and absence of NGF was 105 nM and 4.35 nM, respectively. This suggests that NGF provides protection against thimerosal cytotoxicity. To determine if apoptotic versus necrotic cell death was occurring, oligonucleosomal fragmented DNA was quantified by ELISA. Control levels of fragmented DNA were similar in both the presence and absence of NGF. With and without NGF, thimerosal caused elevated levels of fragmented DNA appearing at 0.01 microM (apoptosis) to decrease at concentrations >1 microM (necrosis). These data demonstrate that thimerosal could alter NGF-induced signaling in neurotrophin-treated cells at concentrations lower than those responsible for cell death. Virginia-Maryland Regional College of Veterinary Medicine, Laboratory for Neurotoxicity Studies, Virginia Tech, 1 Duckpond Drive, Blacksburg, Virginia 24061-0442, USA. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15843506
Havarinasab S, Haggqvist B, Bjorn E, Pollard KM and Hultman P (2005). Immunosuppressive and autoimmune effects of thimerosal in mice. Toxicol Appl Pharmacol 204: 109-21. The possible health effects of the organic mercury compound thimerosal (ethylmercurithiosalicylate), which is rapidly metabolized to ethylmercury (EtHg), have recently been much debated and the effect of this compound on the immune system is largely unknown. We therefore studied the effect of thimerosal by treating A.SW (H-2s) mice, susceptible to induction of autoimmunity by heavy metals, with 10 mg thimerosal/L drinking water (internal dose ca 590 microg Hg/kg body weight/day) for up to 30 days. The lymph node expression of IL-2 and IL-15 mRNA was increased after 2 days, and of IL-4 and IFN-gamma mRNA after 6 and 14 days. During the first 14 days treatment, the number of splenocytes, including T and B cells as well as Ig-secreting cells decreased. A strong immunostimulation superseded after 30 days treatment with increase in splenic weight, number of splenocytes including T and B cells and Ig-secreting cells, and Th2- as well as Th-1-dependent serum immunoglobulins. Antinucleolar antibodies (ANoA) targeting the 34-kDa nucleolar protein fibrillarin, and systemic immune-complex deposits developed. The H-2s strains SJL and B10.S also responded to thimerosal treatment with ANoA. The A.TL and B10.TL strain, sharing background genes with the A.SW and B10.S strain, respectively, but with a different H-2 haplotype (t1), did not develop ANoA, linking the susceptibility to H-2. Thimerosal-treated H-2s mice homozygous for the nu mutation (SJL-nu/nu), or lacking the T-cell co-stimulatory molecule CD28 (B10.S-CD28-/-), did not develop ANoA, which showed that the autoimmune response is T-cell dependent. Using H-2s strains with targeted mutations, we found that IFN-gamma and IL-6, but not IL-4, is important for induction of ANoA by thimerosal. The maximum added renal concentration of thimerosal (EtHg) and inorganic mercury occurred after 14 days treatment and was 81 microg Hg/g. EtHg made up 59% and inorganic mercury 41% of the renal mercury. In conclusion, the organic mercury compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury. Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology (AIR), Linkoping University, SE-581 85 Linkoping, Sweden. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15808517