High positive frequency of antibodies to metallothionein and heat shock protein 70 in sera of patients with metal allergy.

Two principal types of stress protein, heat shock proteins (hsps) and metallothionein (MT), are induced in cells responding to a variety of stresses. They play an important role in protecting cells from these stresses. However, many reports indicate that antibodies to hsps are present in human serum and are associated with several autoimmunity diseases. Metals, which are commonly allergenic to humans, induce both MT and hsp70 (one of the hsps family). Until now, there has been no report of any antibody to MT in human serum. In the present study, serum samples from healthy controls (Group I), and patients suffering from atopic dermatitis without (Group II) or with (Group III) metal allergy, were measured for antibodies to MT and hsp70, using an enzyme-linked immunosorbent assay (ELISA). Metal allergy was confirmed by patch testing. We first found that antibody to MT exists in human serum. We also found a high positive frequency of antibody to MT (51.3%) and to hsp70 (43.6%) in the sera of Group III, compared to those of Group I (3.8% and 5.1%) or Group II (6.4% and 5.1%). Furthermore, there was a strong positive correlation between antibody to MT and antibody to hsp70 in Group III (P = 0.0013), but not in Group I and Group II. Our results indicate that antibody to MT exists in human serum, as do antibodies to hsps, and suggest that elevated levels of MT and hsp70 antibodies are associated with metal allergy in atopic patients.

Long term effects of Toki-shakuyaku-san on brain dopamine and nerve growth factor in olfactory-bulb-lesioned mice.

We used olfactory-bulb-lesioned mice induced by intranasal irrigation with zinc sulfate as a model of dementia, to investigate the effects of Toki-shakuyaku-san (TSS) on monoamines and nerve growth factor (NGF) in brain regions. TSS was given daily through the drinking water for either 1, 2, 3, 4 or 8 weeks from the day after olfactory lesion. The administration of TSS significantly suppressed the decrease of 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in olfactory bulb of olfactory-lesioned mice at 1 week, and tended to suppress the decrease of DOPAC and HVA during the experimental session. However, the administration of TSS had no influence on dopamine contents. NGF contents in the olfactory bulb were increased after the irrigation, and the value returned to the same level as the control at 8 weeks after. Although the NGF contents in the olfactory bulb of TSS-treated mice were immediately increased at 1 and 2 weeks, the value returned to normal level within 3 weeks. These findings indicate that oral administration of TSS prevents the reduction of dopamine metabolites, DOPAC and HVA, and immediately increased NGF contents in the olfactory bulb. This suggested that TSS treatment promotes the NGF contents in olfactory nerves and rescue the neurons from damage.