Suppression of immune response and protective immunity to a Japanese encephalitis virus DNA vaccine by coadministration of an IL-12-expressing plasmid.

IL-12 plays a central role in both innate and acquired immunity and has been demonstrated to potentiate the protective immunity in several experimental vaccines. However, in this study, we show that IL-12 can be detrimental to the immune responses elicited by a plasmid DNA vaccine. Coadministration of the IL-12-expressing plasmid (pIL-12) significantly suppressed the protective immunity elicited by a plasmid DNA vaccine (pE) encoding the envelope protein of Japanese encephalitis virus. This suppressive effect was associated with marked reduction of specific T cell proliferation and Ab responses. A single dose of pIL-12 treatment with plasmid pE in initial priming resulted in significant immune suppression to subsequent pE booster immunization. The pIL-12-mediated immune suppression was dose dependent and evident only when the IL-12 gene was injected either before or coincident with the pE DNA vaccine. Finally, using IFN-gamma gene-disrupted mice, we showed that the suppressive activity of the IL-12 plasmid was dependent upon endogenous production of IFN-gamma. These results demonstrate that coexpression of the IL-12 gene can sometimes produce untoward effects to immune responses, and thus its application as a vaccine adjuvant should be carefully evaluated.

Dimethylformamide-induced liver damage among synthetic leather workers.

Prevalence of liver injury associated with dimethylformamide (DMF) exposure was determined. Medical examinations, liver function tests, and creatine phosphokinase (CPK) determinations were performed on 183 of 204 (76%) employees of a synthetic leather factory. Air concentrations of solvents were measured with personal samplers and gas chromatography. The concentration of DMF in air to which each worker was exposed was categorized. High exposure concentrations of DMF (i.e., 25-60 ppm) were significantly associated with elevated alanine aminotransferase (ALT) levels (ALT greater than or equal to 35 IU/l), a result that did not change even after stratification by hepatitis B carrier status. Modeling by logistic regression demonstrated that exposure to high concentrations of DMF was associated with an elevated ALT (p = .01), whereas hepatitis B surface antigen (HBsAg) was slightly but independently associated with an elevated ALT (p = .07). In those workers who had normal ALT values, there occurred still significantly higher mean ALT and aspartate aminotransferase (AST) activities, especially among those who were not HBsAg carriers. A significant association existed between elevated CPK levels and exposure to DMF. However, an analysis of the CPK isoenzyme among 143 workers did not reveal any specific damage to muscles. This outbreak of liver injury among synthetic leather workers is ascribed to DMF. It is recommended that the occupational standard for DMF and its toxicity among HBsAg carriers be evaluated further.

Manganese induced parkinsonism: an outbreak due to an unrepaired ventilation control system in a ferromanganese smelter.

Several cases of parkinsonism were found in a ferromanganese smelter after the ventilation system had broken down and had not been repaired for eight months in 1985. To determine the aetiology and prevalence of parkinsonism, 132 workers were submitted to thorough medical examination and estimated air concentrations of carbon monoxide and manganese at different worksites. Only six of eight workers performing electrode fixation or welding during 1985 developed parkinsonism. They were exposed for 30 minutes each day, seven days a week, to high concentrations of air manganese (greater than 28.8 mg/m3). There was a consistent trend between the index of exposure to manganese and signs and symptoms exhibited by extrapyramidal systems. After repair of the ventilation system, the air concentration of manganese during electrode fixation and welding decreased to less than 4.4 mg/m3; furthermore, no new cases of parkinsonism have been observed. Workers with parkinsonism recovered partially after removal from original worksites and treatment with levodopa. It is concluded that the outbreak resulted from exposure to high concentrations of manganese fumes through the breakdown of the ventilation system.