J.P. de Groot

Reversal of mucosal tolerance by subcutaneous administration of interleukin‐12 at the site of attempted sensitization

Oral feeding of proteins causes peripheral T‐cell tolerance, as revealed by reduced delayed‐type hypersensitivity (DTH) reactivity after immunization. This type of tolerance can be due both to passive T‐cell anergy and active immunosuppression. Using ovalbumin‐fed mice we studied whether putatively immunostimulatory cytokines could break this state of mucosal tolerance. Cytokines were administered locally at the site of attempted sensitization. It was found that neither interleukin‐2 (IL‐2), interferon‐γ (IFN‐γ) nor granulocyte–macrophage colony‐stimulating factor (GM‐CSF) could restore the response to immunization. In contrast, local administration of IL‐12 at the site of attempted immunization resulted in full recovery of DTH reactivity. The dichotomy between the two Th1 stimulatory cytokines IFN‐γ and IL‐12 was also reflected by different effects on ovalbumin‐specific antibody isotypes. Although both IFN‐γ and IL‐12 downregulated serum IgG1‐levels in tolerant mice, suggesting decreased ovalbumin‐specific Th2 function, only local administration of IL‐12 led to increased serum IgG2a levels. These results support the view that potentiation of Th1 effector function is critical for reversal of mucosal tolerance.

Low allergenicity of clonidine impedes studies of sensitization mechanisms in guinea pig models

During clinical mills, a clonidine transdermal device has been found to induce clonidine‐specific allergic contact dermatitis in up to 25% of patients during a treatment period of 1 year. Using 3 different guinea pig strains, development was attempted of an experimental guinea pig model that would allow for in‐depth studies into the mechanism of sensitization, and a possible role of transdermal device components. Transient low‐level clonidine allergy could be obtained only in a minority of animals, with severe sensitization procedures departing from epicutaneous applications, combined with intradermal (adjuvant) FCA injections. Sensitization was not potentiated by additional booster procedures, including cyclophosphamide pretreatment, nor any of the putative cofactors (UV‐treatments, C. parvum or acetaldehyde involvement) studied. These results suggest that the persistent skin contacts in man with transdermal devices for sustained drug delivery, generate unique conditions favouring the development of allergic contact dermatitis, which are difficult to mimic in experimental animal models. Thus, clinical allergy may develop even lo extremely weak sensitizing drugs that can be safety used orally, and escape most currently available predictive contact allergy animal models Clinical studies remain unavoidable for studying factors that may reduce sensitization rates to more acceptable levels.

Agrarian labour market and technology under different regimes

The downfall in early 1986 of the Haitian dictator Claude Duvalier (&dquo;Baby Doc’) had an interesting side effect that passed largely unnoticed outside the Dominican Republic. The over 15,000 seasonal workers who year after year left Haiti to harvest the sugarcane in the Dominican Republic stayed at home! This decision made it clear once more that contract labor had been crimped, and it highlighted the role the dictator and his repressive apparatus had played in this process. Meanwhile, in the Dominican Republic emergency measures had to be taken: soldiers and government personnel were employed to bring in the harvest. These events raise the question of why a country like the Dominican Republic had become completely dependent on manual labor-and