Effect of cortisol and ACTH on corticosteroid-suppressed peripheral blood natural killer cells from healthy volunteers and patients with Crohn's disease.

Recently, we have shown that administration of adrenocorticotropic hormone (ACTH) to corticosteroid-treated Crohn's disease (CD) patients increased the peripheral blood natural killer (NK) cell activity which was suppressed by the corticosteroids. To elucidate this observation we analysed the in vitro effect of budesonide, prednisolone, cortisol, and ACTH on NK cells of healthy volunteers and corticosteroid-treated CD patients. Incubation of peripheral blood mononuclear cells (PBMNC) from healthy volunteers during the cytotoxicity assay caused a dose-dependent inhibition of NK cell activity by the three corticosteroids, while ACTH had hardly any effect. Pre-incubation for 18 h with high and low inhibiting concentrations also showed a significant inhibiting effect on NK cell activity of the corticosteroids. The percentage of CD56+ NK cells tended to increase after pre-incubation with a high inhibiting concentration of budesonide, prednisolone, and cortisol. Incubation of budesonide- or prednisolone-suppressed PBMNC from healthy volunteers and CD patients, with ACTH and/or cortisol, to mimic the in vivo situation, did not restore the corticosteroid-induced suppression of NK cell activity. The increase of the budesonide- or prednisolone-suppressed NK cell activity after in vivo administration of ACTH to the CD patients is therefore probably not a direct effect of cortisol or ACTH. Presumably other factors like cytokines and/or neurohormones must be involved in the in vivo interaction between corticosteroids, ACTH, and NK cells.

c-Ha-ras oncogene transfection does not affect NK cell sensitivity of human colorectal carcinoma cell lines.

BACKGROUND, MATERIALS AND METHODS: To investigate whether a c-Ha-ras oncogene, pointmutated in codon 12, modulates NK sensitivity of human colorectal tumor cells, this oncogene was introduced in two colorectal carcinoma cell lines, i.e. CaCo2 and SW480. RESULTS: Although transfection with this oncogene increased the levels of c-Ha-ras mRNA (4- to 5-fold) and induced phenotypic and genotypic changes, respectively, in the CaCo2 and SW480 cell lines, the susceptibility to NK cell lysis was only marginally affected. However, CaCo2 and SW480 cell lines transfected with a plasmid containing the wild type of the c-Ha-ras gene were found to be more sensitive to NK cells. CONCLUSIONS: The present study suggests that the sensitivity of human colorectal carcinoma cells to NK cell activity in vitro depends only marginally on the expression of the c-Ha-ras oncogene.

Contribution of plasma cortisol to corticosteroid-suppressed peripheral blood natural killer cell activity in Crohn's disease.

We recently showed that patients with active ileocecal Crohn's disease (CD) have a temporarily suppressed peripheral blood natural killer (NK) cell activity during treatment with oral budesonide or prednisolone. This suppression was caused by a decrease in the number of CD16+ NK cells in the circulation. In the present study we evaluated the contribution of cortisol in plasma to this suppressed NK cell activity. The CD patients took part in a controlled study where they received either oral budesonide or prednisolone for 10 weeks. Before treatment, and at 4 and 10 weeks of treatment, peripheral blood NK cell activity, numbers of circulating CD16+ NK cells, and plasma cortisol levels were analysed. These parameters were determined both before and 30 min after administration of adrenocorticotropic hormone (ACTH). The ACTH-induced plasma cortisol increase was accompanied by a stimulated NK cell activity, when both are suppressed by corticosteroid treatment, without changing the number of CD16+ NK cells. Therefore, a low plasma cortisol level contributes to the corticosteroid mediated NK cell suppression in active ileocecal CD.