Influence of HLA phenotypes on the inhibition of in vitro alloreactivity by cyclosporine.

Interindividual variations in the immunosuppressive effect of Cyclosporine have been observed in clinical organ transplantation. Searching for an in vitro correlate we investigated a possible relation between inhibition of alloresponsiveness by CsA and the HLA phenotypes of the responder or stimulator in mixed lymphocyte reactions. Peripheral blood mononuclear cells from 28 healthy volunteers were used as responder or stimulator cells (gamma-irradiated) and the inhibitory effect of graded amounts of CsA was determined in 130 criss-cross combinations. Sensitivity of alloresponsiveness to the drug was expressed as the dose causing 50% inhibition (ED50) and was read from the inhibition curves generated after four-parameter logistic curve fitting. ED50 ranged from 0.35 ng/ml to 33.4 ng/ml and correlated only weakly with the magnitude of the response (r = 0.12). In MLC with HLA DR4-positive responder cells, ED50 was significantly lower (Pc = 0.0035, Kruskal Wallis) when compared with MLC with responder cells of other DR haplotypes. For HLA DR5-positive responder cells ED50 was significantly higher (Pc = 0.042) when compared with DR5-negative responder cells. No significant correlation between ED50 and any particular haplotype of the stimulator cells could be observed. Sensitivity to CSA did not differ in MLC with 1 or 2 mismatches in the HLA-DR locus. In summary, we found that sensitivity of in vitro alloreactivity was different for particular HLA DR phenotypes, which may have important implications for the immunosuppressive therapy of transplanted patients with cyclosporine.

Investigations on the effect of repeated hair dyeing on sister chromatid exchanges.

The numbers of sister chromatid exchanges (SCE) were determined in the lymphocytes of ten volunteers (males and females) whose hair was dyed 13 times at intervals of 3-5 wk. Each volunteer used throughout the study a single commercial preparation containing a mixture of aminotoluenes, aminophenols and hydroxybenzenes, and in some cases naphthol, as the active ingredients. The findings were compared with those in a control group matched for age and sex. SCE were determined in blood samples taken before the first exposure, after a sham dyeing and after the first three and the last three actual dyeing procedures. Volunteers were carefully screened for disease, for use of medicines and for radiation exposure. Consumption of alcohol was the same in both groups, but there were more smokers in the treated group. No evidence was found of any effect of repeated hair dyeing on the frequency of SCE. In both the controls and in the hair-dyed subjects a slight decrease in SCE was detected during the course of the experiment; this was independent of sex as well as of the dyeing procedure.